Hydrogel, preparation method therefor and use thereof

Abstract

The present invention relates to a medical hydrogel, and in particular to a hydrogel, a preparation method therefor and the use thereof. The preparation method comprises the steps of: completely dissolving polyvinyl alcohol in deionized water to obtain a component A in a clear state; dissolving acrylamide in deionized water, then adding N,N-methylene bisacrylamide and ammonium persulfate, and mixing same until uniform to obtain a component B; and mixing the component A and the component B at a volume ratio of 1:1 and stirring same until the mixture is completely clear and transparent, then adding Ag-ZnO nanoparticles, and finally dropwise adding a tetramethylethylenediamine solution to obtain a hydrogel prepolymer, and curing same to obtain the hydrogel. The hydrogel obtained in the present invention can be applied to an organ model for surgical training, so that the prepared organ model can more accurately simulate the properties of a biological soft tissue to make surgical training more realistic, has a better performance in terms of inhibiting bacteria, anti-fatigue, electric conduction, stretching, compression and the like, and can also be subjected to operations such as electrocoagulation and hemostasis, endoscopy, suturing and cutting.

Description

A hydrogel and its preparation method and application

[0001] This application claims priority from Chinese patent application CN202311407623.6. Technical Field

[0002] The present invention relates to a medical hydrogel, in particular to a hydrogel and a preparation method and application thereof. Background Art

[0003] The increasing difficulty and complexity of surgery has led to the widespread occurrence of medical errors in clinical practice in recent years. Among them, stomach and intestinal diseases have brought medical challenges and generated huge economic costs. There is an urgent need for empirical and high-fidelity gastrointestinal surgery training tools to provide surgical training for surgeons.

[0004] Most current studies use silicone as a raw material, but due to the limitations of its intrinsic physical and chemical properties, silicone cannot solve the common difficulties in the research of surgical training models: First, although silicone can perform routine surgical operations such as cutting and suturing, it cannot correct mechanical properties (such as elastic modulus) and provide a realistic feel of soft biological tissue; Second, silicone cannot simulate the surgical reactions produced by electrosurgical instruments currently used in surgical simulations, such as ultrasonic scalpels, ligasure, and even electrocoagulation effects. For example, electrocoagulation can cause the material to char and thus coagulate and stop bleeding, ultrasonic scalpels can cut solid organs, and coagulate blood vessels. etc.; Third, conventional 3D printing models using various software such as mimics obtain the required STL data by removing the tissues around organs or lesions. However, in actual surgery, these surrounding tissues and vascular branches are the parts that need to be surgically treated in the process of exposing the lesions, which cannot be achieved with silicone; Fourth, surgical operations are all performed along the tissue layer, which requires materials with more subtle physical properties, which is difficult to achieve with current models. This is the difficulty currently faced by 3D printing bionic gradient structured soft models for surgical training, and it is also the key to the application of 3D printing technology in surgery.

[0005] Hydrogels are a class of hydrophilic polymer materials with a three-dimensional (3D) network structure. They are slippery, soft materials whose 3D polymer networks are filled with a large amount of bound water, interfacial water, and free water. Hydrogels exhibit physiological properties similar to those of biological tissues and organs and are widely used in biomedical research. However, anatomical models based on hydrogels for surgical simulation are not widely used in China or abroad.

[0006] In recent years, with the advancement of printing technology and the urgent need for more demanding surgical training models, hydrogels have been gradually applied to surgical training models in a wider range of fields, particularly in surgery. However, the performance of existing hydrogel models still needs to be further improved in many aspects, such as poor temporal stability, susceptibility to microbial invasion, breeding of bacteria and fungi, and difficulty in simulating the surgical responses produced by electrosurgical instruments.

[0007] For example, there is a prior art technology that discloses the use of polyvinyl alcohol (PVA) and plant glue (PHY) to mix and make a composite hydrogel (CH) with viscoelastic response of different soft tissues, showing the flexibility of the composite hydrogel in simulating the interaction between surgical tools and various soft tissues (such as brain, lungs and liver) and the matching of the mechanical properties of pig tissues and organs, but lacks model verification and feedback of real training results. There are also some technical solutions that further use the composite hydrogel to make a brain tissue model for mechanical response under load, which can reproduce the brain displacement phenomenon and the response of brain tissue to depression and palpation, but lacks simulation of neuroanatomical details. In addition, a low-cost ultrasound training model was made using agar gel, which has similar characteristics to human tissue such as sound velocity, impedance and density, but the acoustic attenuation coefficient of agar is lower, the bubbles left during model making are prone to artifacts, and the storage time is not ideal, and other problems have not been well solved. The current cutting-edge international approach proposes the concept of replacing fresh corpses with non-biological material models. By changing the concentration and degree of polymerization of polyvinyl alcohol (PVA) hydrogel to achieve different mechanical properties of various tissues (such as tissue parenchyma kidneys, blood vessels, tumors and fat, etc.), a complete robotic surgery training platform has been constructed, including hydrogel kidneys, surrounding muscles, peritoneum, fat and any other relevant organs defined by the patient's anatomy.

[0008] To overcome the limitations of hydrogels, prior art methods disclose adding 1% chlorhexidine digluconate (used to prevent bacterial and fungal invasion due to its antibacterial properties) to gelatin-based hydrogels to optimize model durability. Alternatively, based on the numerous gel materials proposed for training, a copolymer-oil gel has been proposed as an inert and stable material. Glycerol in the oil-based gel is used as a dispersant to improve the ultrasonic and mechanical properties of the oil-based copolymer model. Two mineral oils of varying viscosities are used to adjust the sample's acoustic velocity, attenuation, backscatter, density, and Young's modulus to within the range of values ​​for different soft tissues used in surgical training. Oil-based gels address the poor temporal stability of water-based gels, reduce biological invasion, and eliminate the need for specialized storage environments. Furthermore, some methods tightly apply hydrocolloid dressings, used as medical bandages for drying and protecting certain types of wounds, to gelatin-based hydrogels. These dressings adhere tightly to the surface of the gelatin matrix, allowing doctors to manipulate the model without damaging the surface. While effective in preventing biological invasion, these methods increase costs, require stringent application conditions, and are difficult to mass-produce.

[0009] It can be seen that the existing hydrogel organ models have defects in Young's modulus, water content, electrical conductivity, stretching, compression, fatigue resistance, and biocompatibility, especially in terms of suturing, cutting, and reactivity of electrosurgical instruments (they cannot simulate the surgical reactions produced by electrosurgical instruments, such as electrocoagulation can cause the material to char and thus coagulate and stop bleeding, and ultrasonic scalpels can be used to cut solid organs and coagulate blood vessels).

[0010] The above-mentioned practical difficulties indicate that it is necessary to develop a new medical hydrogel that can comprehensively consider cost and effectiveness issues, overcome the shortcomings of existing technologies, better simulate surgical organs, and provide a basis for medical research.

[0011] Summary of the Invention

[0012] The present invention aims to solve the deficiencies in surgical training models and preservation in the prior art, and provides a hydrogel and a preparation method and application thereof.

[0013] In order to solve the above technical problems, the present invention is solved by the following technical solutions:

[0014] A first aspect of the present invention provides a method for preparing a hydrogel, comprising the following steps:

[0015] Step (1), preparing component A: completely dissolving polyvinyl alcohol in deionized water to obtain component A in a clear state;

[0016] Step (2), preparing component B: dissolving acrylamide in deionized water, then adding N,N-methylenebisacrylamide and ammonium persulfate, and mixing uniformly to obtain component B;

[0017] Step (3), mixing component A and component B in a volume ratio of 1:1 and stirring until completely clear and transparent, then adding Ag-ZnO nanoparticles, and finally adding tetramethylethylenediamine solution dropwise to obtain a hydrogel prepolymer solution;

[0018] In step (4), the hydrogel prepolymer solution is solidified to obtain the hydrogel.

[0019] Preferably, step (1) is to dissolve polyvinyl alcohol in deionized water, and stir at 90°C for 1-2 hours until the polyvinyl alcohol is completely dissolved and becomes clear, and then cool to room temperature to obtain component A, wherein the mass ratio of polyvinyl alcohol to deionized water is 1:9.

[0020] Preferably, in step (3), the Ag-ZnO nanoparticles are synthesized by a chemical precipitation method, specifically, Zn(Ac)2 and NaOH are dissolved in deionized water respectively, and then mixed and stirred to obtain a mixed solution, and then AgNO3 is added to the mixed solution, and finally the Ag-ZnO nanoparticles are obtained by centrifugation, water washing, alcohol washing and drying.

[0021] Preferably, step (3) specifically includes:

[0022] Step (31), first dissolving Zn(Ac)2 and NaOH in deionized water to obtain a Zn(Ac)2 solution and a NaOH solution, respectively, and then mixing the Zn(Ac)2 solution and the NaOH solution at 65°C and stirring for 2-4 hours to obtain a mixed solution;

[0023] Step (32), then adding AgNO3 to the mixed solution of step (31) and stirring at 90°C for 2-4 hours;

[0024] Step (33), finally, centrifugation, water washing, alcohol washing and drying are carried out in sequence to obtain Ag-ZnO nanoparticles.

[0025] A second aspect of the present invention provides a hydrogel comprising component A, component B and component C, wherein component A comprises polyvinyl alcohol, component B comprises acrylamide, N,N-methylenebisacrylamide and ammonium persulfate, and component C is Ag-ZnO nanoparticles.

[0026] Preferably, the hydrogel is obtained by the method for preparing a hydrogel described in the first aspect of the present invention.

[0027] Preferably, the hydrogel is configured to be used for preparing a hydrogel organ model.

[0028] The third aspect of the present invention provides an application of a hydrogel, wherein the hydrogel described in the first aspect or the second aspect of the present invention is applied to an organ model for surgical training.

[0029] Preferably, the hydrogel is applied to a gastrointestinal model, specifically, the hydrogel prepolymer obtained in step (3) of the first aspect of the present invention is injected into a 3D printed gastrointestinal organ mold prepared in advance through a pouring port until it is full. After component B is gelled, it is placed in a freezer at -20°C and low-temperature frozen for 4-8 hours, then taken out of the freezer, and after being taken out, it is allowed to return to room temperature before being removed from the mold to prepare a hydrogel gastrointestinal model.

[0030] Preferably, the hydrogel is applied to a vascular model, specifically:

[0031] A hollow 3D printed vascular substrate model was obtained using open source software (MIMICS) and computer-aided design (CAD) data.

[0032] Then, the hydrogel prepolymer solution obtained according to step (3) of the first aspect of the present invention is evenly coated on the surface of the 3D printed blood vessel substrate model, and after the coating is completed, it is frozen for 4-8 hours and then taken out to obtain a 3D blood vessel substrate with the outer surface coated with hydrogel;

[0033] Finally, the 3D vascular substrate with the hydrogel coated on the outer surface is dissolved as a whole in an organic solvent such as acetone to obtain a double network hydrogel (DN) 3D vascular model.

[0034] Preferably, the preparation process of the training organ model is as follows: obtaining a medical digital image file of the corresponding organ through computer three-dimensional scanning, extracting and reconstructing the organ model, repairing and refining the extracted organ reconstructed model, completing the mold naming, outputting a mold including a positive mold and a negative mold according to the shape of the organ, designing the support structure and positioning of the mold, and then using a 3D printer to print the mold according to the slice data. After printing, the mold is surface treated and the support structure is removed.

[0035] Due to the adoption of the above technical solution, the present invention has the following significant technical effects:

[0036] (1) The present invention designs a PVA / PAM double-network hydrogel, which can be applied to organ models for surgical training by adjusting the concentration of the hydrogel crosslinker and the amount of Ag-ZnO nanoparticles. The prepared organ model can more accurately simulate the properties of biological soft tissue, making surgical training more realistic, and has good performance in antibacterial, anti-fatigue, electrical conductivity, stretching, compression and other properties. At the same time, it can also perform electrocoagulation hemostasis, endoscopic examination, suturing and cutting and other operations.

[0037] (2) The present invention prepares Ag-ZnO nanoparticles and adds the Ag-ZnO nanoparticles to the hydrogel. By adjusting the amount of Ag-ZnO nanoparticles added, the Young's modulus of the PVA / PAM hydrogel is increased, making the DN elastic hydrogel have better mechanical properties matching the target tissue.

[0038] (3) The present invention enhances the mechanical properties of PVA / PAM hydrogel through a secondary freeze-thaw preparation method, so that the elongation at break and Young's modulus of the hydrogel product prepared by the present invention are close to those of the real human intestine. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] FIG1 is a characterization diagram of Ag-ZnO nanoparticles prepared in Example 4 of the present invention.

[0040] FIG2 is a schematic diagram of the preparation process of the hydrogel training model in Example 6 of the present invention.

[0041] FIG3 is a schematic diagram of the design process of the PVA / PAAm hydrogel in Example 7 of the present invention.

[0042] FIG4 is a schematic diagram of the mechanical properties of the gastrointestinal tissue simulation hydrogel in Example 8 of the present invention.

[0043] FIG5 is a tensile comparison diagram of the gastrointestinal tissue simulation hydrogel and real biological gastrointestinal tissue in Example 8 of the present invention.

[0044] FIG6 is a diagram showing the anti-fatigue performance test and results of the tissue-like soft hydrogel according to Example 9 of the present invention.

[0045] FIG7 is a diagram showing the water content test results of human soft tissues and various organs according to Example 10 of the present invention.

[0046] Figure 8 is a schematic diagram of the water content and water retention (dried at room temperature for 12 hours) of the PVA-AM hydrogel (left) and the PVA-AM@Ag-ZnO hydrogel (right) in Example 10 of the present invention.

[0047] FIG9 is a schematic diagram of the electrical conductivity of PVA and PAM hydrogels in Example 11 of the present invention.

[0048] FIG10 is a diagram showing the structure and physical properties of the hydrogel in Example 11 of the present invention.

[0049] FIG11 is a graph showing the biocompatibility test of the hydrogel in Example 12 of the present invention.

[0050] FIG12 is a schematic diagram of the antibacterial performance of the hydrogel after the introduction of Ag-ZnO in Example 12 of the present invention.

[0051] FIG13 is a schematic diagram of a gastrointestinal anastomosis operation experiment using a hydrogel in Example 13 of the present invention, wherein: (A) a small incision is made in the anterior wall of the stomach; (B) a small incision is made in the distal end of the small intestine; (C) the stapler is placed in the stomach; (D) the intestinal tube is placed in the common anastomosis; (E) the common opening is closed; and (F) the operation is completed.

[0052] FIG14 shows the process and evaluation of the hydrogel blood vessel model simulated bleeding experiment in Example 14 of the present invention. DETAILED DESCRIPTION

[0053] The present invention is further described in detail below with reference to the accompanying drawings and embodiments.

[0054] Example 1: A method for preparing a hydrogel

[0055] This embodiment provides a method for preparing a hydrogel, which comprises the following steps:

[0056] Step (1), preparing component A: completely dissolving polyvinyl alcohol in deionized water to obtain component A in a clear state, wherein the mass ratio of polyvinyl alcohol to deionized water is 1:9;

[0057] Step (2), preparing component B: dissolving acrylamide in deionized water, then adding N,N-methylenebisacrylamide and ammonium persulfate, and mixing uniformly to obtain component B;

[0058] Step (3), mixing component A and component B in a volume ratio of 1:1 and stirring until completely clear and transparent, then adding Ag-ZnO nanoparticles, and finally adding tetramethylethylenediamine solution dropwise to obtain a hydrogel prepolymer solution;

[0059] In step (4), the hydrogel prepolymer solution is solidified to obtain the hydrogel.

[0060] In this embodiment, step (1) is specifically to dissolve 10 g of polyvinyl alcohol in 90 mL of deionized water, and stir at 90° C. for 1-2 hours until the polyvinyl alcohol is completely dissolved and becomes clear, and then cool to room temperature to obtain component A with a mass fraction of 10%.

[0061] In step (2), 40 g of acrylamide was dissolved in 100 mL of deionized water at room temperature, 180 mg of N,N-methylenebisacrylamide (0.3 mol %) and 200 mg of ammonium persulfate (2 mg / mL) were added, and the mixture was mixed to obtain component B.

[0062] In step (3), component A and component B are mixed at a volume ratio of 1:1 and stirred until completely clear and transparent, 0.125% by mass of Ag-ZnO nanoparticles are added and mixed, and finally 200 μL of a 1 μL / mL tetramethylethylenediamine solution is added dropwise and mixed to obtain a hydrogel prepolymer solution;

[0063] In step (4), the hydrogel prepolymer solution is solidified to obtain a hydrogel.

[0064] In addition, in step (3) of this embodiment, the Ag-ZnO nanoparticles are synthesized by a chemical precipitation method, specifically, Zn(Ac)2 and NaOH are dissolved in deionized water, and then mixed and stirred to obtain a mixed solution, and then AgNO3 is added to the mixed solution. Finally, the Ag-ZnO nanoparticles are obtained by centrifugation, water washing, alcohol washing and drying in sequence, which specifically includes:

[0065] Step (31), first dissolving Zn(Ac)2 and NaOH in deionized water to obtain a Zn(Ac)2 solution and a NaOH solution, respectively, and then mixing the Zn(Ac)2 solution and the NaOH solution at 65°C and stirring for 2-4 hours to obtain a mixed solution;

[0066] Step (32), then adding AgNO3 to the mixed solution of step (31) and stirring at 90°C for 2-4 hours;

[0067] Step (33), finally, centrifugation, water washing, alcohol washing and drying are carried out in sequence to obtain Ag-ZnO nanoparticles.

[0068] Example 2: A hydrogel

[0069] This embodiment provides a hydrogel, which is obtained using the preparation method in Example 1.

[0070] Example 3: Application of a hydrogel

[0071] This embodiment provides an application of a hydrogel, in which the hydrogel in Example 2 is applied to an organ model for surgical training.

[0072] The specific applications in this embodiment include the following two:

[0073] (1) The hydrogel is applied to the gastrointestinal model, specifically: the hydrogel prepolymer solution is injected into the 3D printed gastrointestinal organ mold prepared in advance through the pouring port until it is full, and after component B is first gelled due to free radical polymerization, it is placed in a freezer at -20°C and low-temperature frozen for 4-8 hours, and then taken out of the freezer. After being taken out, it is allowed to return to room temperature before being removed from the mold to prepare a hydrogel gastrointestinal model.

[0074] (2) Applying the hydrogel to a vascular model, specifically:

[0075] A hollow 3D printing model is obtained through open source software (MIMICS) and computer-aided design (CAD) data. Specifically, vascular medical imaging data (extracted by MIMICS) is first obtained through computed tomography (CT) angiography or magnetic resonance imaging (MRI) scanning. This data is then converted into a three-dimensional model through computer-aided design (CAD). The vascular part of the model is extracted and converted into 3D printable STL data. The STL data is then used to make a hollow 3D printing model using a soluble 3D printing material through a 3D printer. The vascular medical imaging data obtained through computed tomography (CT) angiography or magnetic resonance imaging (MRI) scanning can be modified to the desired vascular shape, and the diameter of the 3D printing model is determined according to the required diameter of the blood vessel.

[0076] Then, the hydrogel prepolymer solution is evenly coated on the surface of the 3D printed model, and after the coating is completed, it is frozen for 4-8 hours and then taken out to obtain a 3D blood vessel model with the outer surface coated with hydrogel;

[0077] Finally, the 3D blood vessel model with the hydrogel coated on the outer surface was immersed in acetone to dissolve the 3D printed model inside the hydrogel to obtain a hydrogel blood vessel model.

[0078] Example 4: Synthesis and Characterization of Ag-ZnO Nanoparticles

[0079] Ag-ZnO nanoparticles were synthesized by chemical precipitation method. Zn(Ac)2 solution and NaOH solution were mixed and stirred at 65℃ for several hours, then AgNO3 was added and stirred for several hours. The mixture was heated to 90℃ and kept for several hours. The mixture was then washed with deionized water and ethanol and dried in vacuum.

[0080] Ag-ZnO nanoparticles showed regular spherical shapes with varying sizes under transmission electron microscopy (TEM) ( FIG1A ).

[0081] Dynamic light scattering (DLS) results revealed that the prepared Ag-ZnO nanoparticles had an average hydrodynamic diameter of 180 nm. Digital photographs revealed a pale yellow dispersion in water (Figure 1B). X-ray photoelectron spectroscopy (XPS) revealed the various elements in the Ag-ZnO NPs, including a characteristic peak for Zn2p at 1018.0 eV, a peak corresponding to O at 528.5 eV, and a characteristic peak for Ag3d at 365.1 eV (Figure 1C). To further verify the chemical composition of the synthesized nanoparticles, energy-dispersive X-ray spectroscopy (EDS) was used to analyze them, detecting uniform distribution of Ag and Zn elements, confirming the successful synthesis of the Ag-ZnO nanoparticles.

[0082] Example 5: Preparation of a double-network antibacterial hydrogel gastrointestinal model

[0083] A double-network antibacterial hydrogel was prepared using a one-pot free radical polymerization method. The prepolymer solution of the hydrogel was prepared in two parts. Component A: Stir polyvinyl alcohol at 90°C for 1-2 hours until the solid powder was completely dissolved and the solution was clear. Cool to room temperature and set aside. Component B: Dissolve 2M acrylamide in deionized water at room temperature, add 0.3mol% MBA and 2mg / mL APS. Components A and B were mixed in a volume ratio of 1:1 and stirred until completely clear and transparent. Ag-ZnO nanoparticles of various mass fractions (0, 0.025%, 0.05%, 0.075%, 0.1%, 0.125%, 0.15%) were added and mixed thoroughly. Finally, 1μL / mL of TEMED solution was added dropwise and mixed thoroughly to obtain a prepolymer solution. The prepolymer liquid is injected into the 3D printed gastrointestinal organ mold prepared in advance through the pouring port until it is full. After component B is gelled, it is placed in a freezer at -20°C for low-temperature freezing for 4-8 hours and then taken out of the freezer. Depending on the mechanical properties of various organs in the human body, 1-2 freeze-thaw cycles can be performed. After taking it out, wait for it to return to room temperature before removing it from the mold to prepare a gastrointestinal hydrogel organ model.

[0084] Example 6: Preparation of hydrogel training model

[0085] As shown in Figure 2A, medical digital image files were obtained using MIMICS 23.0 software. These files were derived from a 3D computed tomography scan of the human abdomen, and models of the stomach, intestines, and small blood vessels were extracted and reconstructed. The extracted STL files were imported into Magic 24 for repair to obtain a more detailed structure. Because the data structure of hollow organs such as the gastrointestinal tract remains incomplete after repair, OBJ files were exported from Magic 24 and imported into Z Brush for further refinement. Finally, mold design was completed using NX 1899, and positive and negative molds were designed based on the organ's shape. The STL files of the designed molds were imported into Magic 24 for further design of the support structure and positioning. The molds were then printed using an FDM 3D printer based on the slice data. After printing, the molds were surface treated and the support structures removed. We prepared blood vessels by printing small blood vessel models as sacrificial materials and then soaking them in prepolymer solution. Alternatively, organ models such as the stomach and intestine can be prepared using a two-step printing-then-molding method. The relevant model preparation scheme is shown in Figure 2B, and subsequent applications can be performed as shown in Figure 2C.

[0086] Example 7: Design of multifunctional and tunable PVA / PAAm hydrogels

[0087] In order to obtain 3D printed gastrointestinal gel organs with special functions such as conductivity, antibacterial, Young's modulus, water content simulation and anti-fatigue, PVA / PAAm@Ag-ZnO hydrogel (DN hydrogel) was prepared.

[0088] The specific preparation method of DN hydrogel is as follows: a double-network antibacterial hydrogel prepolymer solution is prepared by a one-pot free radical polymerization method (Figure 3A). The hydrogel is completed in two parts: Component A: polyvinyl alcohol is stirred at 90°C for 1-2 hours until the solid powder is completely dissolved and the solution is clear, and then cooled to room temperature for use; Component B: 2M acrylamide is dissolved in deionized water at room temperature, and 0.3 mol% MBA and 2 mg / mL APS are added; Component A and Component B are mixed in a volume ratio of 1:1 and stirred until completely clear and transparent, and Ag-ZnO nanoparticles of various mass fractions (0, 0.025%, 0.05%, 0.075%, 0.1%, 0.125%, 0.15%) are added and mixed evenly, and finally 1 μL / mL TEMED solution is added and mixed evenly to obtain a prepolymer solution.

[0089] The prepolymer solution was poured through the pouring port into a previously prepared 3D-printed gastrointestinal organ mold until full. The mold was kept sealed to prevent water evaporation. After the AM free radical polymerization was complete, the mold was placed in a -20°C freezer. For the freeze / thaw process, the hydrogel was first cooled to -20°C for 8 hours and then thawed at room temperature for 3 hours. This process was repeated one to two times to prepare hydrogels with different desired mechanical properties.

[0090] Based on the crystallization of PVA chains during freeze-thaw cycles, we believe that physical entanglement between PVA and PAAm chains can enhance the crosslinking effect. In addition, the presence of a large number of hydroxyl groups in PVA chains can form hydrogen bonds with the amide groups in PAAm chains, resulting in tight crosslinking (Figures 3B and 3C). The crosslinking points act as stress transfer centers, dissipating energy during deformation of the hydrogel network. The hydrogen bonding interactions provide dynamically reversible exchange points, enhancing its mechanical properties and imparting fatigue resistance. In addition, Ag-ZnO was introduced into the PVA / PAAm hydrogel to impart electrical conductivity and antibacterial properties.

[0091] Example 8: Mechanical and structural characterization of tissue-like soft hydrogels

[0092] For biological tissues including soft tissues (brain, kidney, lung, heart, blood vessels, liver, stomach, intestine, etc.) and hard tissues (bone), the Young's modulus varies from a few Pascals to hundreds of MPa, as shown in Figure 4A. Therefore, elastic hydrogels with tunable stiffness and tissue-like softness are needed to cover the significant mechanical differences between the two. In this example, we explored the mechanical properties of hydrogels by adjusting the content of crosslinker MBA and antibacterial nanoparticles Ag-ZnO.

[0093] The tensile and compressive strengths of systems containing different crosslinkers and varying nanoparticle contents were analyzed using a high-low temperature dual-column testing machine (Instron 5966). The samples were cut into a "dumbbell" shape (16mm×4mm×1mm) using a tablet press and raised from below at a constant rate of 50mm / min. The tensile stress and strain were recorded in real time after the sensor contacted the model. Similarly, in the compression test, cylindrical hydrogel samples (d=8mm, h=8mm) were prepared using an 8mm diameter glass mold and compressed at a rate of 5mm / min, and their compressive properties were measured. Young's modulus was calculated based on the tensile performance parameters.

[0094] First, mechanical characterization was performed to investigate the differences in mechanical properties of the prepared gastric-simulating hydrogels. The mechanical properties of elastic hydrogels can be modulated by varying the chemical crosslinking, specifically the N,N'-methylbisacrylamide (MBA) content. As shown in Figures 4B and 4C, we tested polyvinyl alcohol-polyacrylamide (PVA-PAM) hydrogels with varying crosslinker contents. When the MBA content in the hydrogel network varied between 0.05 and 0.35 mol% (relative to the monomer), the overall Young's modulus of the hydrogels increased and then decreased. Interestingly, when the MBA content exceeded 0.3 mol%, the Young's modulus of the hydrogel decreased from 125.9 ± 6.2 kPa to 90.1 ± 4.5 kPa. This is because excessive crosslinking can cause the crosslinkers within the gel to aggregate, forming large particles or clumps. This results in uneven distribution of the crosslinker within the gel, leading to large defects in localized areas. These large, uneven defects cause stress concentration, affecting the structure and properties of the gel, making it more susceptible to rupture during stretching, thereby reducing the Young's modulus. To approach the Young's modulus of a real stomach, we selected 0.3 mol% of the cross-linker for further in-depth research and introduced Ag-ZnO nanoparticles (Figures 4F, G). However, we found that the introduction of a small amount of Ag-ZnO nanoparticles (0.01-0.1%) reduced the Young's modulus of the PVA-PAM hydrogel to a certain extent. This may be due to complex interactions in the interface region between a small amount of Ag-ZnO nanoparticles and the gel matrix, reducing the effective connection between the molecular chains and resulting in a decrease in the Young's modulus of the gel. However, when the addition of 0.125% Ag-ZnO nanoparticles was added, the Young's modulus of the PVA / PAM hydrogel increased significantly, reaching 166.9±9.kPa, which is close to the Young's modulus of a real human stomach (Figure 4A). This may be because the addition of excessive nanoparticles can fill the gaps and defects in the PVA / PAM hydrogel, increasing the density and strength of the gel, thereby increasing the Young's modulus. On this basis, we further increased the addition amount of Ag-ZnO nanoparticles and verified PVA / PAM hydrogels with addition amounts of 0.15%, 0.175%, and 0.2%. Since the PVA / PAM hydrogel prepolymer will quickly gel within 10 seconds after the addition of Ag-ZnO nanoparticles exceeds 0.15%, it is impossible to perform organ printing by combining direct printing and indirect printing. We set 0.15% as the critical value, and its Young's modulus is actually reduced compared to 0.125%, only 110.3±7.1kPa.

[0095] To further simulate real intestinal tissue, we used a secondary freeze-thaw cycle to enhance the mechanical properties of PVA / PAM hydrogels, aiming to achieve values ​​similar to those of the human intestine in terms of elongation at break and Young's modulus. While pristine polyvinyl alcohol / polyacrylamide (PVA / PAM) hydrogels are typically soft and have low mechanical strength, the mechanical strength of PVA / PAM hydrogels is significantly affected by the number of freeze-thaw cycles. This method is a simple and effective way to improve the mechanical properties of PVA-PAM hydrogels. The tensile strength of the original PVA / PAM hydrogels in different groups was approximately 0.4 MPa, and this was enhanced to some extent after secondary freeze-thaw cycles. In the group with 0.3% MBA content, the tensile strength of the PVA / PAM hydrogel increased to 0.6 MPa, and the Young's modulus increased from 125.96±6.2 kPa to 235.63±6.3 kPa. Surprisingly, the tensile strength and elongation at break of the group containing 0.125% Ag-ZnO nanoparticles approached those of real human intestinal tissue, with an elongation at break of 126.07% (Figure 4H), which is within the range of 145.88±31.51% for real human intestinal tissue. Furthermore, the Young's modulus of the PVA / PAM@Ag-ZnO hydrogel was 463.01±10.63 kPa, also close to that of real organs (Figure 4I).

[0096] To better compare the tensile properties with those of real biological gastrointestinal tissue, we conducted longitudinal tensile tests and Young's modulus tests on real human gastrointestinal tissue (Figure 5). The resulting stress-strain curves were similar to those of the PVA / PAM hydrogel group with 0.125% Ag-ZnO nanoparticle addition and different freeze-thaw cycles, and the corresponding Young's moduli were also relatively close.

[0097] Example 9: Fatigue resistance test of tissue-like soft hydrogel

[0098] In practical applications, hydrogel organ models used in surgical training must withstand repeated friction from surgical instruments. Therefore, the durability and stability of the model are crucial for its success. To this end, we tested the fatigue resistance of the hydrogels of this invention.

[0099] The different modes of twisting and deformation observed in Figures 6A, 6B, and 6C demonstrate that the DN hydrogels of the present invention exhibit excellent flexibility and high deformability, for example, being able to resist strong deformations such as knotting and twisting. Furthermore, upon removal of the compressive force, the hydrogels rapidly return to their original shape, demonstrating excellent shape memory properties. As shown in Figures 6D-6G, after 500 bends, the DN hydrogels retained their initial shape without significant deformation or cracking. These results fully demonstrate the long-lasting stability and excellent bending resistance of the DN hydrogels. Furthermore, to evaluate the fatigue resistance of the DN hydrogels, the DN hydrogels derived from the pure PVA-AM strategy and the DN hydrogels derived from the PVA-AM@Ag-ZnO strategy were subjected to 50 consecutive compression-relaxation cycles to simulate the repeated stress conditions of human tissue at a compressive strain of 50%. The results in Figure 6H indicate that after the first few cycles, the maximum load decreases slightly, then stabilizes and remains virtually unchanged over subsequent cycles. This indicates that DN hydrogel exhibits long-lasting stability and reliable mechanical properties under simulated stress environment, and the addition of Ag-ZnO nanoparticles does not affect its anti-fatigue properties and can even increase its maximum load.

[0100] Example 10: Water content and water retention rate test of tissue-like soft hydrogel

[0101] Many soft tissues and organs in the human body have high water content. As shown in Figure 7A, the intestinal tissue is approximately 70% water, the stomach is approximately 72%, the liver and heart are approximately 75%, the lungs are approximately 80%, the kidneys are approximately 81%, and the brain is as high as 85%. Similarly, we tested the water content of the fabricated hydrogel organ model cubes, whose mechanical properties closely resemble those of real tissues. The calculation method is as follows:

[0102] The prepared hydrogel was freeze-dried and weighed (W0). The dried hydrogel was then immersed in deionized water. The swollen hydrogel was taken out and weighed at a predetermined time (W t ). The water content is given by the following formula:

[0103] As shown in Figures 7B and 7C, we tested PVA-PAM hydrogels with varying crosslinker contents. When the MBA content in the hydrogel network varied between 0.05 and 0.35 mol% (relative to the monomer), the size of the hydrogel blocks gradually decreased. As the crosslinker content increased, the porosity within the gel generally decreased. This means that the microscopic pores within the gel became smaller or more dense, restricting the movement and permeation of water molecules. Consequently, the water content also tended to decrease gradually, from 86±4% to 75±4%. As shown in Figures 7D and 7E, the water content of the PVA-PAM hydrogels subjected to two freeze-thaw cycles remained unchanged, ranging from 86±4% to 755±4%. This indicates that our elastic hydrogels, which exhibit tissue-like softness, also possess tissue-like high water content, enabling them to simulate highly water-rich soft tissues such as the stomach, intestines, and heart. We also tested the water content of DN hydrogel cubes incorporating varying concentrations of Ag-ZnO nanoparticles. As shown in Figures 7F and 7G, the size and water content of the hydrogel cubes remained similar, but a downward trend was observed, with the water content decreasing from 78±4% to 72±4%. We suspect that the higher concentration of nanoparticles creates additional barriers within the gel, hindering the free movement of water molecules. This may result in a reduction in water content within the gel, and therefore a lower water content. Similarly, we tested the water content of PVA-PAM hydrogel cubes incorporating varying concentrations of nanoparticles after two freeze-thaw cycles. The trend remained similar, with the water content ranging from 77±4% to 71±3%. The high concentration of nanoparticles resulted in water contents in PVA-PAM hydrogels after one to two freeze-thaw cycles approaching those of real human gastrointestinal tissue, effectively mimicking the physiological interactions between biological soft tissues and organs.

[0104] We also tested the water content and water retention of the DN hydrogels after drying at room temperature for different times. Figure 8 shows that after drying for 12 hours at room temperature, the water content and water retention of the pure PVA-AM hydrogel were above 65% and 60%, respectively. Similarly, the water content and water retention of the PVA-AM@Ag-ZnO hydrogel were still above 65% and 60%, respectively, demonstrating that our designed PVA-AM@Ag-ZnO hydrogel has good water retention properties.

[0105] Example 11: Structure and physical properties testing of tissue-like soft hydrogel

[0106] In order to investigate whether there are interactions between the components in the PVA-AM@Ag-ZnO hydrogel, we characterized its chemical structure by Fourier transform infrared spectroscopy. As shown in the FTIR spectrum (Figure 10A), the stretching vibration peaks of the NH groups of the PVA-AM and the added nanoparticles are both at 3270 cm -1 , and there is no obvious movement; the stretching vibration peaks of the two groups of amide bonds are both at 1660 cm -1, and there was no obvious movement, indicating that the added Ag-ZnO nanoparticles had no obvious interaction with the DN hydrogel components.

[0107] In addition to excellent mechanical properties and highly simulated water content, the electrical conductivity of the hydrogel plays an indispensable role in the operation of electronic surgical instruments based on hydrogel organ models. As shown in Figure 9, pure PVA hydrogel shows 5.63×10 -5 s / m, and the pure PAM hydrogel also showed a low conductivity of 4.29×10 -5 s / m. The conductivity of DN hydrogel was improved by introducing Ag-ZnO nanoparticles into it (Figure 10B). When PVA and AM formed DN hydrogel, its conductivity increased to 7.19×10 -4 s / m. When PAM and PVA are combined to form a double network hydrogel, its conductive properties may be improved due to the special structure of the two materials intertwined with each other. When 0.01% by mass of nanoparticles are introduced, the conductivity of the PVA-AM@Ag-ZnO (0.01%) hydrogel system shows 8.79×10 -2 s / m, which is 120.23 times that of pure DN hydrogel, 1560.13 times that of pure PVA hydrogel, and 2040.90 times that of pure PAM hydrogel. In addition, as the concentration of Ag-ZnO nanoparticles increases from 0.01% to 0.15%, the conductivity of the hydrogel also changes significantly from 8.79×10 -2 s / m increased to 1.72×10 -1 s / m. In addition, the PVA-AM@Ag-ZnO (0.125%) hydrogel system also showed excellent electrical conductivity of 1.65×10 -1 s / m, which can well simulate the conductivity of the real human gastrointestinal tract. The main reason is that silver with excellent conductive properties plays a major conductive role. In addition, the conductivity of pure PVA hydrogel is very small and almost negligible.

[0108] Furthermore, the tissue-like softness of PVA-AM@Ag-ZnO and pure PVA-AM hydrogels, due to their high water content and excellent wettability, significantly reduces friction. Therefore, both hydrogels effectively reduce frictional resistance when in contact with other surfaces or tissues. This friction-reducing property makes hydrogels very useful in applications that simulate tissue movement or contact with biological organisms. As shown in Figure 10C, the friction coefficient of pure PVA-AM hydrogel is between 0.06 and 0.08, while the friction coefficient of PVA-AM@Ag-ZnO hydrogel is slightly higher, at around 0.12. This is due to the Ag-ZnO nanoparticles on the surface increasing the friction of the hydrogel. Despite this increase in friction, the overall friction coefficient remains low. When the hydrogel is subjected to external pressure or load, water is squeezed out, forming a lubricating layer that reduces direct contact with other surfaces. This lubricating layer allows the hydrogel to slide more easily under load, reducing the friction coefficient and exhibiting excellent sliding properties. These characteristics facilitate a more realistic experience when training surgical instruments on models.

[0109] To verify the viscoelastic properties of the tissue-like elastic hydrogel, we conducted rheological tests (Figure 10D). In the experiment, we performed a rheological frequency sweep to explore the dynamic mechanical behavior of the hydrogel samples. By observing the rheological frequency sweep results of the hydrogel simulating the stomach and intestine, we found that the hydrogel samples exhibited a typical viscoelastic response.

[0110] Throughout the frequency range, we observed that the storage modulus (G') of the two groups of hydrogels was always higher than the loss modulus (G"), which means that the hydrogel has higher elastic properties, demonstrating the solid-like elastic properties of the hydrogel. (Figure 10E and Figure 10F) The indicator tanδ (G" / G') in viscoelasticity calculations is a commonly used parameter to describe viscoelastic properties. By calculating tanδ, we can evaluate the viscoelastic characteristics of tissue-mimicking hydrogels and further reveal their applicability in tissue-like simulations. The viscoelasticity of the simulated hydrogel gastrointestinal tissue in the PVA-AM@Ag-ZnO system is between 0.01207-0.17586, which is between 0.1-0.45 of the natural gastrointestinal tissue / organ, indicating that the hydrogel has flow properties close to those of living gastrointestinal tissue. In contrast, the viscoelasticity of the simulated hydrogel gastrointestinal tissue in the pure PVA-AM system is below 0.01633, and the viscoelasticity is different from that of biological soft tissue.

[0111] Example 12: Biocompatibility test of tissue-like soft hydrogel

[0112] In order to evaluate the biosafety of tissue-like elastic hydrogels during surgical training, we used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) to evaluate the in vitro cell compatibility of four types of hydrogels. The results are shown in Figure 11. Figure 11A shows the cell survival rate of L929 cells after co-culture for 7 days in the simulated gastric hydrogel group (PVA-PAM hydrogel with one freeze-thaw cycle), the simulated gastric hydrogel group with 0.125% mass fraction of Ag-ZnO nanoparticles added, the simulated intestinal hydrogel group (PVA-PAM hydrogel with one freeze-thaw cycle), and the simulated intestinal hydrogel group with 0.125% mass fraction of Ag-ZnO nanoparticles added using 7-day hydrogel extracts of different concentrations; Figure 11B shows the live and dead cell fluorescence microscopy images of L929 cells in the TCP group, the simulated gastric hydrogel group (PVA-PAM hydrogel with one freeze-thaw cycle), the simulated gastric hydrogel group with 0.125% mass fraction of Ag-ZnO nanoparticles added, the simulated intestinal hydrogel group (PVA-PAM hydrogel with one freeze-thaw cycle), and the simulated intestinal hydrogel group with 0.125% mass fraction of Ag-ZnO nanoparticles added.

[0113] We evaluated the viability of L929 mouse fibroblasts by co-culturing them with hydrogel extracts of varying concentrations for 7 days to observe the cell viability. As shown in Figure 11, the survival rate of L929 cells was significantly correlated with the addition of 0.125% Ag-ZnO nanoparticles, while the cell viability was slightly decreased compared to the group without nanoparticles. The cell viability of L929 cells incubated for 7 days in the extract of a 100 mg / mL hydrogel immersing for 7 days in simulated gastric fluid and 0.125% Ag-ZnO nanoparticles was 87.4 ± 2.13%, and the cell viability of L929 cells incubated for 7 days in the extract of a 100 mg / mL hydrogel immersing for 7 days in simulated intestinal fluid and 0.125% Ag-ZnO nanoparticles was 89.54 ± 2.26%. The cell viability of L929 cells in the remaining groups all exceeded 90%, indicating that the various tissue-elastic hydrogels have low cytotoxicity. According to ISO 10993-5-2016, cell viability of more than 80% can be considered as non-cytotoxic.

[0114] In addition, the cytotoxicity of different hydrogel materials was evaluated by live / dead experiments (Figure 11B). L929 mouse fibroblasts were labeled with calcein-AM (green) and PI (red) fluorescent dyes to observe the distribution of living and dead cells. Under a fluorescence microscope, the TCP group, Stomach hydrogel group, Stomach@Ag-ZnO hydrogel group, Intestines hydrogel group, and Intestines@Ag-ZnO hydrogel group all showed strong green fluorescence signals corresponding to living cells. The bright red fluorescence signals representing dead cells were relatively small in all five groups, once again proving that various tissue elastic hydrogels have low cytotoxicity.

[0115] Bacterial infection and fungal contamination are among the problems that need to be addressed in biomedical materials. Traditional hydrogels can quickly absorb and store large amounts of water due to their water absorption. This makes hydrogels an ideal environment for mold growth, and hydrogels are usually composed of organic or polymer compounds, which may contain some nutrients required for mold growth. These organic substances can become a nutrient source for mold growth, thereby promoting the growth of mold. Here, we studied the antibacterial properties of PVA-AM@Ag-ZnO DN strategy hydrogels against Escherichia coli and Staphylococcus aureus. The Ag-ZnO introduced in the present invention has good antibacterial properties (see Figure 12). The DN hydrogel with added Ag-ZnO has a significant inhibition zone relative to the pure DN hydrogel.

[0116] Example 13: Gastrointestinal anastomosis experiment using tissue-like soft hydrogel

[0117] It is crucial for junior residents to practice gastrointestinal anastomosis before operating on a patient. The maneuverability of the model is a key evaluation metric. A high-quality model should be able to simulate actual surgical resections and a variety of complex situations for operator skill training and surgical planning. By providing realistic scenarios and challenges, this maneuverability effectively improves the surgeon's operational skills in actual surgery, with suturing, knot tying, and dissection techniques being key skills.

[0118] The present invention provides realistic and reusable gastrointestinal tissue hydrogel models for surgical training. As shown in Figure 17, a gastric model was prepared using a PVA-AM@Ag-ZnO hydrogel formulation that underwent a single freeze-thaw cycle, and an intestinal model was prepared using a PVA-AM@Ag-ZnO hydrogel formulation that underwent a double freeze-thaw cycle.

[0119] We invited a gastrointestinal surgeon with experience performing over 500 gastrointestinal anastomoses to perform the model (Figures 13A-13F). The entire simulated gastrointestinal anastomosis procedure was smooth, stable, and completed successfully. After the experiment, the expert noted that the texture, size, color, and feel of the model's sutures closely resembled those found in real-life settings. The expert, therefore, endorsed the model's use as a simulation tool for educating surgeons.

[0120] Example 14: Bleeding and hemostasis simulation and hydrogel evaluation experiment of vascular-like soft hydrogel

[0121] Intraoperative bleeding is a common and crucial step in surgical procedures, especially during the resection of tumors and lesions in the gastrointestinal tract, where varying degrees of bleeding may occur. Promptly controlling bleeding points is crucial to preventing severe blood loss and ensuring patient safety.

[0122] In order to simulate the coagulation and hemostasis process of blood vessels, we designed and prepared blood vessel models with different inner diameters (2 mm and 3 mm). The method for preparing the blood vessel models can be used as described in Example 3.

[0123] To more realistically simulate the surgical environment, we also simulated bleeding and tested vascular permeability using an external fluid circulation pump (Figures 14A-14D). We also used an ultrasonic scalpel to coagulate and scab the bleeding clots. As shown in Figures 14E-14F, a 2 mm blood vessel formed a good blood clot.

[0124] We invited five surgeons to participate in the evaluation of the validity of hydrogel models, commercially available silicone models, and porcine ex vivo organs (Figure 14G). This evaluation included face validity, content validity, technical authenticity, construct validity, and biosafety validity. Face validity evaluates the model's external appearance, including its appearance, user interface, and interactive design, to determine whether it is attractive, easy to use, and understand. Evaluation criteria may include the user's intuitive experience with the interface, the aesthetics of the interface, and the results of usability tests. Content validity evaluates whether the content provided by the model is accurate, complete, relevant, and able to meet user needs. Evaluation criteria may include assessments of content accuracy, timeliness, information content, and reliability. Technical authenticity evaluates whether the technical methods, algorithms, or simulations used in the model are consistent with real-world conditions and can accurately simulate the target subject or situation. Evaluation criteria may include model accuracy, simulation authenticity, data reliability, and verifiability. Construct validity evaluates whether the model's organizational structure and system architecture are reasonable and clear, and whether they can support the model's stable operation and scalability. Evaluation criteria may include considerations such as system stability, scalability, ease of maintenance and updating. Biosafety effectiveness: Biosafety effectiveness evaluates whether the biomaterials or bioprocesses involved in the model are safe and will not cause harm to humans, animals or the environment. Evaluation criteria may include considerations such as toxicity testing of biomaterials, risk assessment of bioprocesses, and the completeness of biosafety measures. The results are shown in Figure 18G, showing that the hydrogel model and porcine ex vivo organs received good scores in all effectiveness criteria. This is due to their commendable realism in manual operation and structural accuracy, indicating that they have basic effectiveness in training. In addition, because porcine organs are susceptible to microbial contamination in vitro, their biosafety effectiveness scores are relatively low. In contrast, both hydrogel and silicone models have high biosafety scores.

[0125] It is easy to understand that those skilled in the art can combine, split, reorganize, etc. the embodiments of the present application based on one or several embodiments provided in the present application to obtain other embodiments, and these embodiments do not exceed the scope of protection of the present application.

[0126] In short, the above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made according to the scope of the patent application of the present invention should fall within the scope of the patent of the present invention.

Claims

1. A method for preparing a hydrogel, characterized in that: It includes the following steps: Step (1), preparing component A: completely dissolving polyvinyl alcohol in deionized water to obtain component A in a clear state; Step (2), preparing component B: dissolving acrylamide in deionized water, then adding N,N-methylenebisacrylamide and ammonium persulfate, and mixing well to obtain component B; Step (3), mixing component A and component B at a volume ratio of 1:1 and stirring until completely clear and transparent, then adding Ag-ZnO nanoparticles, and finally dropping tetramethylethylenediamine solution to obtain a hydrogel prepolymer solution; In step (4), the hydrogel prepolymer solution is solidified to obtain a hydrogel.

2. The method for preparing a hydrogel according to claim 1, characterized in that: Step (1) specifically comprises dissolving polyvinyl alcohol in deionized water, stirring at 90° C. for 1-2 hours until the polyvinyl alcohol is completely dissolved and becomes clear, and then cooling to room temperature to obtain component A, wherein the mass ratio of polyvinyl alcohol to deionized water is 1:

9.

3. The method for preparing a hydrogel according to claim 1, characterized in that: In step (3), the Ag-ZnO nanoparticles are synthesized by chemical precipitation method, specifically, Zn(Ac)2 and NaOH are dissolved in deionized water respectively, then mixed and stirred to obtain a mixed solution, and then AgNO3 is added to the mixed solution, and finally, the Ag-ZnO nanoparticles are obtained by centrifugation, water washing, alcohol washing and drying.

4. The method for preparing a hydrogel according to claim 3, characterized in that: Step (3) specifically includes: Step (31), first dissolving Zn(Ac)2 and NaOH in deionized water to obtain a Zn(Ac)2 solution and a NaOH solution, respectively, and then mixing the Zn(Ac)2 solution and the NaOH solution at 65°C and stirring for 2-4 hours to obtain a mixed solution; Step (32), then adding AgNO3 to the mixed solution of step (31) and stirring at 90°C for 2-4 hours; Step (33), finally, centrifugation, water washing, alcohol washing and drying are performed in sequence to obtain Ag-ZnO nanoparticles.

5. The method for preparing a hydrogel according to claim 1, characterized in that: The addition ratio of the Ag-ZnO nanoparticles is 0.125%-0.15% by mass.

6. A hydrogel, characterized in that: The invention comprises component A, component B and component C. Component A comprises polyvinyl alcohol, component B comprises acrylamide, N,N-methylenebisacrylamide and ammonium persulfate, and component C is Ag-ZnO nanoparticles.

7. A hydrogel according to claim 6, characterized in that: The mass percentage of component C is 0.125%-0.15%.

8. A hydrogel according to claim 6, characterized in that: The hydrogel is obtained by the preparation method of the hydrogel according to any one of claims 1 to 4.

9. The hydrogel according to claim 6, characterized in that: The Ag-ZnO nanoparticles are prepared by the method described in claims 3-4.

10. The hydrogel according to claim 6, characterized in that: The invention is configured for preparing hydrogel organ models.

11. An application of a hydrogel, characterized in that: The hydrogel according to claim 5 is applied to a training organ model.

12. The use of the hydrogel according to claim 11, characterized in that: The hydrogel is applied to a gastrointestinal model, specifically: According to the method described in claim 1, a hydrogel prepolymer is prepared, and the hydrogel prepolymer is injected into a 3D printed gastrointestinal organ mold prepared in advance through a pouring port until it is full. After component B is gelled, it is placed in a -20°C freezer for low-temperature freezing for 4-8 hours, and then taken out of the freezer. After being taken out, it is waited to be restored to room temperature and can be removed from the mold to prepare a hydrogel gastrointestinal model.

13. The use of the hydrogel according to claim 11, characterized in that: The hydrogel is applied to a blood vessel model, specifically: A hollow 3D printed vascular substrate model was obtained using open source software (MIMICS) and computer-aided design (CAD) data; Then evenly coat the surface of the 3D printed vascular substrate model The hydrogel prepolymer solution prepared according to the method of claim 1 is frozen for 4-8 hours after coating, taken out, and restored to room temperature to obtain a 3D vascular substrate; Finally, the 3D vascular substrate is dissolved as a whole in an organic solvent to obtain a double-network hydrogel 3D vascular model.

14. The use of the hydrogel according to claim 10, characterized in that: The preparation process of the training organ model is as follows: obtaining a medical digital image file of the corresponding organ through computer three-dimensional scanning, extracting and reconstructing the organ model, repairing and refining the extracted organ reconstruction model, completing the mold naming, outputting a mold including a positive mold and a negative mold according to the shape of the organ, designing the support structure and positioning of the mold, printing the mold according to the slice data using a 3D printer, and performing surface treatment on the mold and removing the support structure after printing.

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