Hydrogel mesangial model with empty heart blood vessel structure as well as preparation method and application of hydrogel mesangial model

Abstract

The invention discloses a hydrogel system membrane model with an empty heart blood vessel structure as well as a preparation method and application thereof, and the hydrogel system membrane model is characterized by being formed by a reaction system comprising the following components in parts by weight: 8-12 parts of polyvinyl alcohol, 1.5-2.5 parts of ethylene vinyl alcohol, 8-12 parts of N-hydroxymethyl acrylamide and 1-4 parts of polyethylene glycol diacrylate, 0.15-0.25 part of a photoinitiator, and the balance of a mixed solvent, totaling 100 parts; the mixed solvent is a solution formed by mixing a polar organic solvent and deionized water according to a volume ratio of 6: 4 to 8: 2; the preparation method comprises the following steps: dissolving polyvinyl alcohol and ethylene vinyl alcohol in stages through an n-propyl alcohol / water mixed solvent system, introducing hydroxymethyl acrylamide to prepare a dual cross-linked network, and preparing a hydrogel model by combining a photocuring process under the wavelength of 405nm. The invention has the beneficial effects of high fidelity reduction of mesenteric blood vessel morphology with water resistance and adhesion, excellent mechanical properties and thermal stability, and suitability for clinical training.

Description

Technical Field

[0001] The present invention belongs to the field of surgical training models, and specifically relates to a hydrogel mesangial model with a hollow vascular structure, a preparation method and its application, especially a hydrogel mesangial model suitable for medical teaching, surgical training, preoperative simulation exercises and medical device testing, a preparation method and its application. Background Art

[0002] The current field of surgical training faces a dual dilemma: a shortage of models. Traditional biological models, subject to stringent ethical review and limited access, suffer from short shelf life (typically less than 72 hours), high single-use costs (approximately $2,000 per case), the risk of biocontamination, and incompatibility with robotic training systems. Commercially available physical models also suffer from technical shortcomings, including material mechanics distortion (Young's modulus deviations of 60%-80%), lack of dynamic response (e.g., lack of simulation of heat conduction in electrosurgical instruments), missing tissue layers (only simulating 3-4 tissue types), and low modularity (reusability less than 30%). As a result, 78% of residents are unable to complete advanced minimally invasive surgical training during their training.

[0003] The hydrogel model has unique advantages and can effectively overcome the limitations of traditional models. Its materials can simulate a variety of tissue types, have good biocompatibility and adjustable mechanical properties, and the Young's modulus can be adjusted according to needs, which is close to the real physical properties of human tissue. At the same time, the hydrogel model has a long shelf life and can be used repeatedly, avoiding the contamination risk and high cost of biological models. In addition, the hydrogel model is compatible with the robotic system, supporting more sophisticated surgical simulation training and improving the skills of residents. However, the existing hydrogel models have the following two problems: First, it is impossible to prepare small hollow structures, and the model is too simple. For example, the invention of the large intestine hydrogel organ model can provide an innovative solution for colorectal surgery training, and more realistically simulate the complex operations during surgery. Patent CN109333881 B discloses a biomimetic large intestine and its preparation method. While this biomimetic large intestine possesses the morphology and physiological structure of a real human large intestine and can realistically simulate the digestive environment within the human large intestine, it lacks the mesentery surrounding the large intestine, a crucial component of surgery. Mesenteric dissection must be completed before surgery, a crucial step for comprehensive surgical training. By incorporating a mesenteric layer into the hydrogel model and accurately simulating the dissection process, trainees can experience the realistic anatomy of the mesentery and master dissection techniques, thereby improving surgical precision and safety, ensuring comprehensive and practical training. The mesenteric model includes hollow vascular structures, making its preparation extremely difficult. Secondly, it suffers from poor thermal stability. High-temperature energy instruments (<100°C, such as electrosurgical tips) are commonly used in minimally invasive surgeries such as laparoscopy, which utilize thermal effects to achieve tissue cutting and hemostasis. However, current hydrogel models cannot maintain structural integrity under the operation of high-temperature energy instruments, making them unsuitable for surgical simulation training in electrosurgery and heat-sensitive areas.

[0004] Therefore, there is an urgent need for a hydrogel mesenteric model that can not only restore the mesenteric vascular morphology with high fidelity but also has excellent mechanical properties and thermal stability suitable for clinical training. Summary of the Invention

[0005] In view of the shortcomings of the existing technology mentioned above, the present application provides a hydrogel mesangial model with a hollow vascular structure that restores the mesenteric vascular morphology with high fidelity, has excellent mechanical properties, good thermal stability and is suitable for clinical training, as well as a preparation method and application thereof.

[0006] To solve the above problems, the technical solution adopted in this application is:

[0007] The present invention provides a hydrogel mesangial model with a hollow vascular structure, which is formed by a reaction system comprising the following components in parts by weight: 8-12 parts of polyvinyl alcohol (PVA), 1.5-2.5 parts of ethylene-vinyl alcohol copolymer (EVOH), 8-12 parts of N-hydroxymethyl acrylamide (NHMA), 1-4 parts of polyethylene glycol diacrylate (PEGDA), 0.15-0.25 parts of a photoinitiator, and a mixed solvent supplemented to 100 parts; wherein the mixed solvent is a solution formed by mixing a polar organic solvent and deionized water in a volume ratio of 8:2 to 6:4.

[0008] As a preference of the present application, the polyethylene glycol diacrylate is 1.5-2.5 parts.

[0009] As a preference of the present application, the polyethylene glycol diacrylate is 2 parts.

[0010] As a preference of the present application, the polar organic solvent is one or a combination of methanol, ethanol, n-propanol, and isopropanol.

[0011] As a preference of the present application, the polar organic solvent is n-propanol.

[0012] As a preference of the present application, the volume ratio of the mixed solvent of n-propanol and deionized water is 7:3.

[0013] As a preference of the present application, the photoinitiator is lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP).

[0014] As a preference of the present application, it is formed by a reaction system comprising the following components in parts by weight: 10 parts of polyvinyl alcohol, 2 parts of ethylene-vinyl alcohol copolymer, 10 parts of N-hydroxymethyl acrylamide, 2 parts of polyethylene glycol diacrylate, 0.2 parts of lithium phenyl-2,4,6-trimethylbenzoyl phosphinate, and a mixed solvent supplemented to 100 parts; wherein the mixed solvent is a solution formed by mixing n-propanol and deionized water in a volume ratio of 7:3.

[0015] As a preference of the present application, the Young's modulus of the hydrogel membrane model is 0.04-0.2 MPa; and the elongation at break is between 342.7% and 170%.

[0016] As a preference of the present application, the diameter of the vascular lumen in the hollow vascular structure in the hydrogel mesangium model is controlled between 1-5 mm, and the error of the vascular bifurcation angle is less than 3°.

[0017] As a preferred embodiment of the present invention, the polyvinyl alcohol is low-viscosity PVA with a viscosity range of 44-50 cps, and more preferably, polyvinyl alcohol 0588 low-viscosity type (PVA-205).

[0018] As a preference of the present application, the ethylene content of the EVOH resin is 20% to 45%. More preferably, the ethylene content of the EVOH resin is about 44%.

[0019] The present invention also provides a method for preparing a hydrogel mesangial model having a hollow vascular structure, comprising the following steps:

[0020] Step 1, preparing a mixed solvent: mixing a polar organic solvent and deionized water in a volume ratio of 1:10 to 10:1 to prepare a mixed solvent;

[0021] Step 2, weighing raw materials: weighing 8-12 parts of polyvinyl alcohol, 1.5-2.5 parts of ethylene-vinyl alcohol copolymer, 8-12 parts of N-hydroxymethyl acrylamide, 1-4 parts of polyethylene glycol diacrylate, 0.15-0.25 parts of photoinitiator and the required mixed solvent to make up to 100 parts by weight;

[0022] Step 3: Constructing a high-temperature phase step by step: adding polyvinyl alcohol to a mixed solvent, stirring and reacting at a reaction temperature of 70-90° C. for 1-3 hours to obtain a homogeneous solution; then adding ethylene-vinyl alcohol copolymer to the homogeneous solution, stirring and reacting for a second time at the same temperature for 1-5 hours until completely dissolved, to obtain reaction solution A;

[0023] Step 4: Stepwise low-temperature functionalization: Cool reaction solution A to 30-50°C once, add N-hydroxymethyl acrylamide, and stir to react for 10-60 minutes to obtain reaction solution B; then cool reaction solution B to 20-30°C twice, add polyethylene glycol diacrylate, and stir to react for 5-20 minutes to obtain reaction solution C;

[0024] Step 5, photocuring molding: Add photoinitiator to reaction solution C, ultrasonically disperse for 1-5 minutes, then inject into the mold, photocuring under ultraviolet light for 3-5 minutes, and demolding after curing to obtain a hydrogel mesangial model with a hollow vascular structure.

[0025] As a preferred embodiment of the present application, in step 1, ultrasonic defoaming treatment is performed after the mixed solvent is prepared.

[0026] As a preference of the present application, in step 3, the reaction temperature is 80°C.

[0027] As a preference of the present application, in step 3, the first stirring reaction time is 2 hours, and the second stirring reaction time is 3 hours.

[0028] As a preference of the present application, in step 4, the temperature is lowered to 40° C. at one time and the stirring reaction time is 30 min.

[0029] As a preference of the present application, in step 4, the temperature is lowered to 25° C. for the second time and the stirring reaction time is 10 min.

[0030] As a preference of the present application, in step 5, the wavelength of the ultraviolet light is 405 nm, the light curing time is 5 min, and the ultrasonic dispersion time is 3 min.

[0031] As a preferred embodiment of the present application, the mold in step 5 is a 3D printed mold, which is made of low-toughness brittle photosensitive resin material with a breaking strength of less than 10 MPa. It can be quickly demolded by knocking without affecting the surface quality of the hydrogel, so as to achieve physical knocking demolding without damaging the hydrogel surface.

[0032] The present invention also provides a hydrogel mesangial model with a hollow vascular structure or the use of the hydrogel mesangial model with a hollow vascular structure prepared by the preparation method in medical teaching, surgical training, preoperative simulation exercises and medical device testing.

[0033] As a preferred embodiment of the present application, the applications include but are not limited to suturing, hemostasis, electrocoagulation, ultrasonic scalpel and other advanced surgical instrument operations, robot-assisted surgical systems and laparoscopic training systems.

[0034] As a preferred embodiment of the present application, the applications include but are not limited to laparoscopic mesenteric dissection, vascular anastomosis, tumor resection path planning training and first aid skills drills.

[0035] The reaction mechanism of this application is as follows: by constructing a n-propanol / water mixed solvent system, dissolving polyvinyl alcohol (PVA) and ethylene-vinyl alcohol copolymer (EVOH) in stages, and introducing hydroxymethyl acrylamide (NHMA) to form a double cross-linked network, combined with a photocuring process at a wavelength of 405nm, a highly realistic hydrogel model with excellent water-proofing, adhesion, thermal stability, and mechanical properties was successfully prepared. Then, by using a brittle photosensitive resin 3D printed fragmentable mold, the vascular structure was completely demolded. The model's inner lumen was smooth and dimensionally precise, significantly improving anatomical fidelity and operational realism. Polyvinyl alcohol (PVA) is the main network material of the hydrogel, providing mechanical strength and swelling stability; after high-temperature dissolution, a homogeneous continuous phase is formed, laying the foundation for the three-dimensional structure; the ethylene chain segment of ethylene-vinyl alcohol copolymer (EVOH) improves the anti-swelling property of the hydrogel, optimizes the morphological stability of the hollow vascular structure, and improves the hydrophobic performance. Then, at high temperature, it interpenetrates with PVA through hydrogen bonds, synergistically forming a composite physical network to assist in the directional formation of vascular channels during phase separation; N-hydroxymethylacrylamide (N-HMA) is a dual-functional monomer: the hydroxymethyl (-CH2OH) acts as a cross-linking site to undergo Michael addition reaction with PEGDA, and the amide group (-CONH) can enhance hydrophilicity and promote cell adhesion; N-hydroxymethylacrylamide (NHMA) is precisely grafted to the PVA-EVOH chain under low temperature conditions, and the hydroxymethyl of N-HMA and the hydroxyl of the PVA / EVOH chain react with each other. The base undergoes condensation reaction to introduce cross-linking active sites. The reason for maintaining low temperature is to effectively avoid self-condensation of hydroxymethyl. After further cooling, PEGDA is added. PEGDA serves as a photocrosslinking bridge and plays a key role. The diacrylate group of PEGDA and the hydroxymethyl group of NHMA form a reversible covalent bond through Michael addition reaction to construct a photosensitive prepolymer. Then the photoinitiator phenyl-2,4,6-trimethylbenzoylphosphinate is introduced. Phenyl-2,4,6-trimethylbenzoylphosphinate is excited by ultraviolet light to produce free radicals, which trigger the irreversible copolymerization of the acrylate group of PEGDA and the hydroxymethyl group of NHMA to form a three-dimensional chemical cross-linking network. The mixed solvent dissolves PVA / EVOH at high temperature, and low temperature assists phase separation and solidification. The solvent polarity is controlled to drive the separation of the polymer-rich phase and the lean phase to form a through vascular channel, and finally a hydrogel membranous model with a hollow vascular structure is obtained.

[0036] Compared with the prior art, the present invention has the following advantages:

[0037] 1. High structural simulation and restoration: Combining image modeling and 3D printing mold refinement technology, it can highly restore the distribution morphology and spatial course of microvessels in the mesentery, forming a realistic vascular cavity. It is widely used in the training of surgical procedures such as mesenteric dissection, vascular ligation, and lymph node dissection.

[0038] 2. Adjustable mechanical properties and surgical adaptability: The constructed hydrogel dual network consists of a PVA / EVOH physical network and an NHMA / PEGDA chemical cross-linking network. While maintaining the hydrogel's high water retention and softness, it also imparts an adjustable elastic modulus (40-204 kPa) and elongation at break (>250%), enabling realistic simulation of surgical responses such as abdominal traction, clamping, and suturing.

[0039] 3. Safe and efficient demolding process: Demolding is accomplished by breaking the resin mold, without the need for solvents or high-temperature treatment, preventing pore collapse or adhesion within the hydrogel. The molded model has a completely enclosed vascular cavity, significantly improving the model's fidelity and mechanical integrity.

[0040] 4. Excellent thermal stability, supporting simulation of various surgical procedures and compatibility with instruments: The model is compatible with a variety of surgical instruments, including staplers, electrocoagulation scalpels, and ultrasonic scalpels. It can maintain structural integrity, especially for simulation training scenarios involving electrosurgery and heat-sensitive areas involving high-temperature energy instruments (<100°C, such as the tip of an electrosurgical scalpel). Simulation training can also be combined with intraoperative image navigation systems and robot-assisted surgery systems to enhance trainees' precise understanding of the operation path and surgical anatomy.

[0041] 5. Rapid personalization and batch molding capabilities: By combining medical image modeling (CT / MRI) with photosensitive mold manufacturing processes, the entire model preparation cycle can be shortened to less than 24 hours, simultaneously meeting the dual needs of mass production of standard teaching models and personalized simulation;

[0042] 6. The hydrogel mesangial model with a hollow vascular structure not only significantly improves the model's simulation level and clinical adaptability, but also realizes the organic integration of material function and structural engineering. It provides an effective technical path to solve the current problems in surgical training, such as model deficiency, unrealistic feedback, and insufficient biomimetic degree. It has broad application prospects in teaching, training, and medical device verification. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 Schematic diagram of the preparation of the hydrogel membrane model of the present invention.

[0044] Figure 2 The figures are electron micrographs of cross-sections of hydrogels obtained in the examples of the present invention, wherein (A), (E); (B), (F); (C), (G); (D), (H) are electron micrographs of 100 μm and 50 μm cross-sections of hydrogels with different amounts of cross-linking agent PEGDA, respectively.

[0045] Figure 3Graphs showing the mechanical properties of hydrogels obtained in accordance with an embodiment of the present invention. (A) and (C) are the tensile stress and compressive stress data for different cross-linker concentrations, respectively; (B) and (D) are the tensile modulus and compressive modulus data for different cross-linker concentrations, respectively.

[0046] Figure 4 Graph showing rheological data of hydrogels obtained in an embodiment of the present invention, where (A) and (B) are the storage modulus and loss modulus, respectively; (C) is the viscoelasticity of the hydrogel; and (D) is the friction coefficient.

[0047] Figure 5 This is the rheological diagram of the hydrogel obtained in the embodiment of the present invention at 80°C.

[0048] Figure 6 (A) Thermogravimetric analysis (TGA) and (B) differential scanning calorimetry (DSC) obtained for the examples of the present invention.

[0049] Figure 7 This is a water vapor transmission rate test chart obtained in an embodiment of the present invention.

[0050] Figure 8 This is a data chart of the water retention rate of the hydrogel obtained in an embodiment of the present invention at room temperature for 6 hours.

[0051] Figure 9 This is the infrared spectrum of the hydrogel obtained in the embodiment of the present invention after drying.

[0052] Figure 10 and Figure 11 This is a film-forming mold printed with transparent resin according to the present invention. DETAILED DESCRIPTION

[0053] The following describes the implementation of the present application through specific embodiments. Those skilled in the art can easily understand the other advantages and effects of the present application from the content disclosed in this specification. The present application can also be implemented or applied through other different specific embodiments, and the details in this specification can be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present application.

[0054] It should be noted that the process equipment or devices not specifically specified in the following embodiments are all conventional equipment or devices in the art.

[0055] Furthermore, it should be understood that the one or more method steps mentioned in the present invention do not exclude the presence of other method steps before or after the combination step, or the insertion of other method steps between these explicitly mentioned steps, unless otherwise specified. It should also be understood that the combination connection relationship between one or more devices / apparatuses mentioned in the present invention does not exclude the presence of other devices / apparatuses before or after the combination device / apparatus, or the insertion of other devices / apparatuses between two explicitly mentioned devices / apparatuses, unless otherwise specified. Furthermore, unless otherwise specified, the numbering of each method step is merely a convenient tool for identifying each method step, and is not intended to limit the order of arrangement of each method step or to define the scope of the present invention. Changes or adjustments to their relative relationships, without substantially changing the technical content, should also be considered within the scope of the present invention.

[0056] The following describes the technical solutions of the invention through specific examples. It should be understood that to ensure experimental uniformity, the polyvinyl alcohol, ethylene-vinyl alcohol copolymer, N-methylolacrylamide, polyethylene glycol diacrylate, n-propanol, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate used in each example were all from the same batch. Furthermore, it should be noted that the numbering of each method step serves not only as a convenient tool for identifying the method steps but also limits the order in which the examples are arranged, with the goal of verifying the feasibility of continuous recycling and replication in actual production processes.

[0057] In the following examples of the present application, the polyvinyl alcohol was purchased from Aladdin with a product number of 9002-89-5; the ethylene-vinyl alcohol copolymer (EVOH resin) was purchased from Changchun Petrochemical Co., Ltd. in Taiwan, China with a product number of EVASIN EV4405F; the N-hydroxymethyl acrylamide was purchased from Aladdin with a product number of 924-42-5; the polyethylene glycol diacrylate was purchased from Aladdin with a product number of 26570-48-9; the n-propanol was purchased from Sinopharm Group with a product number of 71-23-8; and the lithium phenyl-2,4,6-trimethylbenzoylphosphinate was purchased from Shanghai Yinchang New Materials Co., Ltd. with a product number of 85073-19-4.

[0058] The present application is further described below in conjunction with specific embodiments, but the protection scope of the present application is not limited thereto.

[0059] The present invention provides a hydrogel mesangial model with a hollow vascular structure, which is formed by a reaction system comprising the following components in parts by weight: 8-12 parts of polyvinyl alcohol (PVA), 1.5-2.5 parts of ethylene-vinyl alcohol copolymer (EVOH), 8-12 parts of N-hydroxymethyl acrylamide (NHMA), 1-4 parts of polyethylene glycol diacrylate (PEGDA), 0.15-0.25 parts of a photoinitiator, and a mixed solvent supplemented to 100 parts;

[0060] The mixed solvent is a solution of n-propanol and deionized water in a volume ratio of 8:2 to 6:4.

[0061] Example 1

[0062] The present invention provides a method for preparing a hydrogel mesangial model with a hollow vascular structure, comprising the following steps:

[0063] Step 1: Prepare a mixed solvent: mix n-propanol and deionized water in a volume ratio of 7:3 to prepare a mixed solvent;

[0064] Step 2, weighing raw materials: weighing by weight 10g polyvinyl alcohol (PVA), 2g ethylene-vinyl alcohol copolymer (EVOH), 10g N-hydroxymethyl acrylamide (NHMA), 1g polyethylene glycol diacrylate (PEGDA), 0.2g lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) and the required mixed solvent to make up to 100g;

[0065] Step 3: Constructing a high-temperature phase step by step: adding polyvinyl alcohol to a mixed solvent, stirring and reacting at a reaction temperature of 80° C. for 2 hours to obtain a homogeneous solution; then adding ethylene-vinyl alcohol copolymer to the homogeneous solution, stirring and reacting for a second time at the same temperature for 3 hours until completely dissolved, to obtain reaction solution A;

[0066] Step 4: Stepwise low-temperature functionalization: Reaction solution A was cooled to 40°C once, N-hydroxymethyl acrylamide was added, and the mixture was stirred and reacted for 30 minutes to obtain reaction solution B; reaction solution B was cooled to 25°C a second time, polyethylene glycol diacrylate was added, and the mixture was stirred and reacted for 10 minutes to obtain reaction solution C;

[0067] Step 5, photocuring: Add lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) to reaction solution C, ultrasonically disperse for 3 minutes, and then inject it into the mold (the mold is a transparent resin brittle mold made by 3D printing) using a syringe pump. Photocuring is carried out under ultraviolet light for 5 minutes. After curing is completed, the mold is broken for demolding to obtain a hydrogel mesangial model with a hollow vascular structure.

[0068] The hydrogel membrane model prepared in this example was characterized and tested as follows:

[0069] (1) Morphological characterization:

[0070] The obtained hydrogel is soft and gel-like. The SEM image is attached. Figure 2 (A) and (E) show that its pores are uniform but the cross-linked network is sparse.

[0071] (2) Mechanical properties:

[0072] The mechanical properties of the hydrogel membrane model prepared in this embodiment were tested. Figure 3 As shown in the figure, the Young's modulus is 0.04 MPa and the elongation at break is about 342.6%, which is suitable for simulating the thin film tissue on the surface of organs.

[0073] Example 2

[0074] This example differs from Example 1 in that the amount of polyethylene glycol diacrylate (PEGDA) used is different, namely 2 g (PEGDA mass concentration is 2%). The rest of the process is exactly the same.

[0075] Example 3

[0076] This example differs from Example 1 in that the amount of polyethylene glycol diacrylate (PEGDA) used is different, namely 3 g. The rest of the process is exactly the same.

[0077] Example 4

[0078] This example differs from Example 1 in that the amount of polyethylene glycol diacrylate (PEGDA) used is different, namely, 4 g. The rest of the process is exactly the same.

[0079] Example 5

[0080] The difference between this embodiment and embodiment 2 is that the amount of ethylene-vinyl alcohol copolymer (EVOH) used is different, that is, the amount of ethylene-vinyl alcohol copolymer (EVOH) used is 2g. The rest of the process is exactly the same.

[0081] Example 6

[0082] The difference between this embodiment and embodiment 1 is that the mixed solvent ratio is different, and the mixed solvent is a solution formed by mixing n-propanol and deionized water in a volume ratio of 8:2. The rest of the process is exactly the same.

[0083] Example 7

[0084] The difference between this embodiment and embodiment 1 is that the mixed solvent ratio is different, and the mixed solvent is a solution formed by mixing n-propanol and deionized water in a volume ratio of 6:4. The rest of the process is exactly the same.

[0085] Example 8

[0086] The present invention provides a method for preparing a hydrogel mesangial model with a hollow vascular structure, comprising the following steps:

[0087] Step 1: Prepare a mixed solvent: mix n-propanol and deionized water in a volume ratio of 9:1 to prepare a mixed solvent;

[0088] Step 2, weighing raw materials: weighing 8 g of polyvinyl alcohol, 1.5 g of ethylene-vinyl alcohol copolymer, 8 g of N-hydroxymethyl acrylamide, 1 g of polyethylene glycol diacrylate, 0.15 g of lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and the required mixed solvent to make up to 100 g by weight;

[0089] Step 3: Constructing a high-temperature phase step by step: adding polyvinyl alcohol to a mixed solvent, stirring and reacting at a reaction temperature of 70° C. for 3 hours to obtain a homogeneous solution; then adding ethylene-vinyl alcohol copolymer to the homogeneous solution, stirring and reacting for a second time at the same temperature for 5 hours until completely dissolved, to obtain reaction solution A;

[0090] Step 4: Stepwise low-temperature functionalization: Reaction solution A was cooled to 30°C once, N-hydroxymethyl acrylamide was added, and the mixture was stirred and reacted for 60 minutes to obtain reaction solution B; reaction solution B was cooled to 20°C a second time, polyethylene glycol diacrylate was added, and the mixture was stirred and reacted for 20 minutes to obtain reaction solution C;

[0091] Step 5, photocuring: Add lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) to reaction solution C, ultrasonically disperse for 3 minutes, and then inject it into the mold (the mold is a transparent resin brittle mold made by 3D printing) using a syringe pump. Photocuring is carried out under ultraviolet light for 5 minutes. After curing is completed, the mold is broken for demolding to obtain a hydrogel mesangial model with a hollow vascular structure.

[0092] Example 9

[0093] The present invention provides a method for preparing a hydrogel mesangial model with a hollow vascular structure, comprising the following steps:

[0094] Step 1: Prepare a mixed solvent: mix n-propanol and deionized water in a volume ratio of 5:5 to prepare a mixed solvent;

[0095] Step 2, weighing raw materials: weighing by weight 12 g of polyvinyl alcohol, 2.5 g of ethylene-vinyl alcohol copolymer, 8 g of N-hydroxymethyl acrylamide, 4 g of polyethylene glycol diacrylate, 0.25 g of lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and the required mixed solvent to make up to 100 g;

[0096] Step 3: Constructing a high-temperature phase step by step: adding polyvinyl alcohol to a mixed solvent, stirring and reacting at a reaction temperature of 90° C. for 1 hour to obtain a homogeneous solution; then adding ethylene-vinyl alcohol copolymer to the homogeneous solution, stirring and reacting for a second time at the same temperature for 1 hour until completely dissolved, to obtain reaction solution A;

[0097] Step 4: Stepwise low-temperature functionalization: Reaction solution A was cooled to 50°C once, N-hydroxymethyl acrylamide was added, and the mixture was stirred and reacted for 10 minutes to obtain reaction solution B; reaction solution B was cooled to 30°C a second time, polyethylene glycol diacrylate was added, and the mixture was stirred and reacted for 5 minutes to obtain reaction solution C;

[0098] Step 5, photocuring: Add lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) to reaction solution C, ultrasonically disperse for 3 minutes, and then inject it into the mold (the mold is a transparent resin brittle mold made by 3D printing) using a syringe pump. Photocuring is carried out under ultraviolet light for 5 minutes. After curing is completed, the mold is broken for demolding to obtain a hydrogel mesangial model with a hollow vascular structure.

[0099] Comparative Example 1

[0100] The difference between this comparative example and Example 1 is that EVOH is removed, and the rest of the processes are exactly the same.

[0101] Comparative Example 2

[0102] The difference between this comparative example and Example 1 is that polyethylene glycol diacrylate (PEGDA) is replaced by N,N′-methylenebisacrylamide (MBAA), and the rest of the process is exactly the same.

[0103] Comparative Example 3

[0104] This comparative example differs from Example 1 in that 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (I2959) is used in place of lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). The remaining processes are identical.

[0105] Comparative Example 4

[0106] The difference between this comparative example and Example 1 is that NHMA is removed. The rest of the processes are exactly the same.

[0107] Comparative Example 5

[0108] The difference between this comparative example and Example 1 is that dimethyl sulfoxide (DMSO) is used instead of the mixed solvent. The rest of the process is exactly the same.

[0109] Comparative Example 6

[0110] This comparative example differs from Example 1 in that step 4 is different. Step 4 is performed using a one-step low-temperature functionalization method. Specifically, reaction solution A is cooled to 40°C once, N-hydroxymethyl acrylamide is added, and the mixture is stirred and reacted for 30 minutes to obtain reaction solution B. Polyethylene glycol diacrylate is then added and stirred and reacted for 10 minutes to obtain reaction solution C. The remaining processes are identical.

[0111] The properties of the hydrogel membrane model prepared in Example 2 are as follows: Figure 3 (A) and (C) are the tensile stress and compressive stress data of different crosslinker concentrations, respectively. Figure 3 (D) and (B) show that the compression modulus and Young's modulus are increased to 0.16 MPa and 0.11 MPa respectively. Figure 2 Compared with the 1% PEGDA concentration in Example 1, (B) and (F) are slightly denser, but not significantly so, while maintaining good flexibility. The simulation effect is closer to the structure of the mesenteric marginal area.

[0112] The performance of the hydrogel membrane model prepared in Example 3 is as follows: the compressive strength of the obtained model is increased to 1.2 MPa, with good load-bearing capacity but slightly hard and brittle. Figure 2 Compared with Examples 1 and 2, the gaps in (C) and (G) are significantly smaller, the structure is more compact, and they are suitable for simulating the pulling part of the instrument, and the elongation at break is reduced to 248%.

[0113] The transparency of the hydrogel prepared in Example 4 was slightly reduced. Figure 2 (D) and (H) show that its microstructure is extremely compact with almost no macropores. Figure 3 Mechanical testing of the model (B) showed a Young's modulus of 0.2 MPa, the highest of all groups; however, its ductility was reduced, with a tensile elongation at break of only 169%. This model is suitable for simulating the mid-axial region of blood vessels, where vascular tension is high.

[0114] The hydrogel prepared in Example 5 showed better thermal stability and shear resistance. Figure 7 As shown in the figure, its water vapor transmission rate has dropped significantly to 1949 g / m 2 ·24h, and subsequently with the increase of EVOH concentration, its water vapor transmission rate does not decrease significantly, and with the increase of concentration, its toughness will gradually decrease, so the optimal content is 2%.

[0115] The hydrogels successfully prepared in Example 6 and Example 7 both formed double-network hydrogels, but the dissolution time needed to be longer, or the dissolution temperature needed to be increased to 90° C. to ensure that PVA and EVOH were fully dissolved.

[0116] Properties of the hydrogels prepared in Examples 8 and 9

[0117] The performance of the hydrogel membrane model prepared in Comparative Example 1 is as follows: this group has no EVOH, and the network lacks the physical entanglement of EVOH and PVA. The toughness of the hydrogel is better, and the tensile strain can reach more than 500%, but the strength is very low, with a Young's modulus of only 0.03MPa. Figure 7The water vapor transmission rate is shown to be 2759 g / m 2 ·24h.

[0118] In Comparative Example 2, polyethylene glycol diacrylate (PEGDA) was replaced with N,N′-methylenebisacrylamide (MBAA). The compression modulus and Young's modulus of the prepared product were 0.07 MPa and 0.03 MPa, respectively, which were lower than those of the hydrogel product prepared in Example. MBAA had low cross-linking efficiency, uneven structure, and poor mechanical properties, and was not recommended as a substitute for PEGDA.

[0119] In Comparative Example 3, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (I2959) was used to replace lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). The compression modulus and Young's modulus of the prepared product were 0.06 MPa and 0.028 MPa, respectively, which were lower than those of the hydrogel product prepared in Example 1. Since the cross-linking density of the hydrogel induced by LAP is higher, a more uniform network structure can be formed, thereby improving the Young's modulus.

[0120] In Comparative Example 4, NHMA was removed, and the compression modulus and Young's modulus of the prepared product were 0.05 MPa and 0.025 MPa, respectively, which were lower than those of the hydrogel product prepared in the example. Since N-hydroxymethylacrylamide (NHMA) was precisely grafted to the PVA-EVOH chain under low temperature, the hydroxymethyl group of N-HMA reacted with the hydroxyl group of the PVA / EVOH chain to introduce cross-linking active sites. The reason for maintaining low temperature is that the self-condensation of the hydroxymethyl group can be effectively avoided, and it can work synergistically with other ingredients in the formula. The prepared product is composed of a PVA / EVOH physical network and an NHMA / PEGDA chemical cross-linking network. While maintaining high water retention and softness of the hydrogel, it is given an adjustable elastic modulus (40-204 KPa) and elongation at break (>250%), which can truly simulate surgical feedback such as abdominal traction, clamping, and suturing.

[0121] The compression modulus and Young's modulus of the product prepared in Comparative Example 5 were 0.03 MPa and 0.015 MPa, respectively. DMSO inhibited the photocuring reaction, and the network structure was incomplete.

[0122] The compression modulus and Young's modulus of the product prepared in Comparative Example 6 are 0.04 MPa and 0.02 MPa, respectively. Adding in sequence helps to form an ordered cross-linked structure, while the one-step method easily leads to unevenness.

[0123] Attachment Figure 4 For the hydrogel ratio of Example 5, Figure 4 (A) and (B) are storage modulus and loss modulus respectively. Figure 4 (C) is the viscoelasticity of the hydrogel. Figure 4(D) in the figure represents the friction coefficient. Changing only the PEGDA content revealed that the hydrogel's storage modulus G' and loss modulus G" increased significantly with increasing PEGDA concentration, demonstrating greater overall mechanical rigidity and network integrity. A decrease in the viscoelastic ratio G" / G' indicates a gradual shift from a soft and plastic material to a rigid and elastic one, making it more suitable for high-intensity manipulation sites such as the mesangial root and vascular traction areas. Friction test results demonstrate the material's excellent surface lubricity and its ability to maintain low friction over an extended period after initial run-in, supporting repeated instrument manipulation training.

[0124] Attachment Figure 5 With attached Figure 6 The hydrogel prepared in Example 2, wherein Figure 5 The rheological properties of the hydrogel at high temperature of 80°C still maintain a high storage modulus (G′> 80,000 Pa), and the loss modulus also has a significant response (G″> 25,000Pa), indicating that it has good high-temperature mechanical stability and viscoelastic synergy. Figure 6 (A) in the figure shows the thermogravimetric analysis data, which indicates that the main thermal decomposition temperature of the material is above 150°C and it completely decomposes between 300–450°C, indicating good thermal stability. It is safe to use under high-temperature instruments (<100°C, such as the tip of an electrosurgical knife) commonly used in surgical simulations. Figure 6 (B) shows its differential scanning calorimetry curve, indicating that the material may experience enhanced molecular segmental mobility and slight changes in viscoelasticity at temperatures between 60 and 80°C. No significant endothermic or exothermic reactions were observed, demonstrating overall structural stability with no significant degradation or melting. When used below 80°C (e.g., in simulated body cavity or electrosurgery environments), the material maintains good thermodynamic stability. These findings demonstrate that the material maintains structural integrity even in high-temperature energy instrumentation environments, making it suitable for surgical simulation training in electrosurgery and heat-sensitive areas.

[0125] Attachment Figure 8 A disc prepared from the hydrogel obtained in Example 2 was tested for water retention at room temperature and 35-41% relative humidity. The hydrogel disc sample maintained a moisture content exceeding 83.7% for 6 hours, demonstrating excellent water retention and suitability for open or prolonged surgical training environments, ensuring the stability of the model's tactile feel and mechanical properties.

[0126] Attachment Figure 9 This is the infrared spectrum of the hydrogel prepared in Example 2 after drying. The FTIR spectrum of the hydrogel sample is at 1664.8 cm -1 A significant C=O stretching vibration peak was observed at 3303.9 cm -1There is a broad O–H / N–H absorption peak nearby, which originates from the hydrophilic groups of PVA and NHMA. Combined with the peak position shift in the region, it shows that the photocrosslinking reaction occurred smoothly and formed a stable three-dimensional network structure.

[0127] In summary, this application achieves high-fidelity reproduction of mesenteric vascular morphology by constructing a dual-network synergistic structure (a physical network formed by the composite of PVA and EVOH, and a chemical network formed by photocrosslinking NHMA and PEGDA) and optimizing the photocuring fabrication process. This hydrogel mesenteric model exhibits excellent mechanical properties and stability suitable for clinical training, significantly enhancing surgical feedback and training simulation. This hydrogel mesenteric model exhibits water-insulating, adhesive, and highly realistic properties. While maintaining the hydrogel's high water retention and softness, it also possesses an adjustable elastic modulus (40-204 kPa) and elongation at break (>250%), enabling realistic simulation of surgical responses such as abdominal retraction, clamping, and suturing. Furthermore, the molded model completely seals the vascular lumen, significantly improving model fidelity and mechanical integrity. The material's primary thermal decomposition onset temperature is above 150°C, with complete decomposition between 300–450°C, demonstrating its excellent thermal stability. It is safe for use with high-temperature instruments (<100°C, such as electrosurgical tips) commonly used in surgical simulations.

[0128] The above examples are for the purpose of illustrating the embodiments disclosed in the present application and are not to be construed as limiting the present application. In addition, the various modifications listed herein and the variations of the methods and compositions in the invention will be apparent to those skilled in the art without departing from the scope and spirit of the present application. Although the present application has been specifically described with reference to various specific preferred embodiments of the present application, it should be understood that the present application should not be limited to these specific embodiments. In fact, various modifications apparent to those skilled in the art as described above to obtain the invention will fall within the scope of the present application.

Claims

1. A hydrogel mesangial model with a hollow vascular structure, characterized in that: The invention is formed by a reaction system comprising the following components in parts by weight: 8-12 parts of polyvinyl alcohol, 1.5-2.5 parts of ethylene-vinyl alcohol copolymer, 8-12 parts of N-hydroxymethyl acrylamide, 1-4 parts of polyethylene glycol diacrylate, 0.15-0.25 parts of a photoinitiator, and a mixed solvent supplemented to 100 parts; wherein the mixed solvent is a solution formed by mixing a polar organic solvent and deionized water in a volume ratio of 8:2 to 6:

4.

2. The hydrogel mesangial model with a hollow vascular structure according to claim 1, characterized in that: The polar organic solvent is one or a combination of methanol, ethanol, n-propanol, and isopropanol.

3. The hydrogel mesangial model with a hollow vascular structure according to claim 1, wherein: The photoinitiator is lithium phenyl-2,4,6-trimethylbenzoylphosphinate.

4. The hydrogel mesangial model with a hollow vascular structure according to claim 1, wherein: The polyethylene glycol diacrylate is 1.5-2.5 parts.

5. The hydrogel mesangial model with a hollow vascular structure according to claim 1, wherein: The invention is formed by a reaction system comprising the following components in parts by weight: 10 parts of polyvinyl alcohol, 2 parts of ethylene-vinyl alcohol copolymer, 10 parts of N-hydroxymethyl acrylamide, 2 parts of polyethylene glycol diacrylate, 0.2 parts of lithium phenyl-2,4,6-trimethylbenzoylphosphinate, and a mixed solvent supplemented to 100 parts; wherein the mixed solvent is a solution formed by mixing n-propanol and deionized water in a volume ratio of 7:

3.

6. A method for preparing a hydrogel mesangial model having a hollow vascular structure according to any one of claims 1 to 5, characterized in that: The following steps are involved: Step 1, preparing a mixed solvent: mixing a polar organic solvent and deionized water in a volume ratio of 1:10 to 10:1 to prepare a mixed solvent; Step 2, weighing raw materials: weighing 8-12 parts of polyvinyl alcohol, 1.5-2.5 parts of ethylene-vinyl alcohol copolymer, 8-12 parts of N-hydroxymethyl acrylamide, 1-4 parts of polyethylene glycol diacrylate, 0.15-0.25 parts of photoinitiator, and the required mixed solvent to make up to 100 parts; wherein the mixed solvent is a solution formed by mixing a polar organic solvent and deionized water in a volume ratio of 1:10 to 10:1; Step 3: Constructing a high-temperature phase step by step: adding polyvinyl alcohol to a mixed solvent, stirring and reacting at a reaction temperature of 70-90° C. for 1-3 hours to obtain a homogeneous solution; then adding ethylene-vinyl alcohol copolymer to the homogeneous solution, stirring and reacting for a second time at the same temperature for 1-5 hours to obtain reaction solution A; Step 4: Stepwise low-temperature functionalization: Cool reaction solution A to 30-50°C once, add N-hydroxymethyl acrylamide, and stir to react for 10-60 minutes to obtain reaction solution B; then cool reaction solution B to 20-30°C twice, add polyethylene glycol diacrylate, and stir to react for 5-20 minutes to obtain reaction solution C; Step 5, photocuring molding: Add photoinitiator to reaction solution C, ultrasonically disperse for 1-5 minutes, then inject into the mold, photocuring under ultraviolet light for 3-5 minutes, and demolding after curing to obtain a hydrogel mesangial model with a hollow vascular structure.

7. The preparation method according to claim 6, characterized in that: In step 3, the reaction temperature is 80° C.; the first stirring reaction time is 2 hours, and the second stirring reaction time is 3 hours.

8. The preparation method according to claim 6, characterized in that: In step 4, the temperature was lowered to 40° C. and stirred for 30 min; the temperature was lowered to 25° C. and stirred for 10 min.

9. The preparation method according to claim 6, characterized in that: In step 5, the wavelength of the ultraviolet light is 405 nm, the light curing time is 5 min, and the ultrasonic dispersion time is 3 min.

10. Use of the hydrogel mesangial model with a hollow vascular structure according to any one of claims 1 to 5 in medical teaching, surgical training, preoperative simulation exercises, and medical device testing.

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