A method of making and products of high strength hydrogels

Abstract

The application discloses a preparation method and product of a high-strength hydrogel, and comprises the following steps: sequentially performing centrifugation, condensation and photocuring on a hydrogel precursor solution, performing progressive cyclic stretching training and PBS immersion treatment on the photocured hydrogel, and finally standing in a sulfate solution to obtain the high-strength hydrogel; the stretching training is performed in the sulfate solution; the above cycle is composed of multiple rounds of stretching training and PBS immersion treatment, one or multiple adjacent rounds of stretching training and PBS immersion treatment form a group of sub-cycles, and the stretching strain of the stretching training in each group of sub-cycles is greater than that of the stretching training in the last group of sub-cycles. The preparation method of the high-strength hydrogel is convenient to operate, low in cost and high in efficiency, and provides a new way for the high-strength scene application of the hydrogel in the fields of regenerative medicine and tissue engineering.

Description

Technical Field

[0001] This invention belongs to the field of biomaterial manufacturing technology, specifically relating to a high-strength hydrogel, its preparation method, and the product. Background Technology

[0002] Hydrogels, as three-dimensional materials composed of hydrophilic polymer networks, have become a research hotspot in the fields of biomedicine and flexible electronics due to their ability to absorb large amounts of water and mimic the mechanical properties of biological tissues. Early hydrogels were represented by polyacrylamide (PAM) and polyvinyl alcohol (PVA), which provided the basic structure through covalent cross-linking. However, their mechanical properties were weak, and they were prone to fracture under stress, limiting their application in the repair of load-bearing tissues or in dynamic devices.

[0003] Patent document CN116966340A (publication date: 2023-10-31) discloses a high-strength, highly biocompatible, and tough hydrogel. This document describes repeatedly stretching a hydrogel in a sulfate solution. The hydrogel is one of the bio-hydrogels such as gelatin or hyaluronic acid, and can be either cured or uncured (for uncured hydrogels, cross-linking and curing are performed after multiple cycles of loading). The hydrogel has a water content of 50-95%, the sulfate solution concentration is 40-60%, and the number of stretching cycles is 10-30. Afterward, it is immersed in PBS solution for 30-180 seconds, with each immersion constituting one loading cycle. The number of loading cycles is 1-30, and the stretching rate of the hydrogel in the sulfate solution is 2-7 mm / min. The hydrogel prepared by this method is named GBTH, and its tensile strength is 6.67 MPa, which is 145 times that of the untreated gel (initial hydrogel).

[0004] Additionally, the literature (3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration, Ke Yao, Gaoying Hong, Ximin Yuan, Weicheng Kong, Pengcheng Xia, Yuanrong Li, Yuewei Chen, Nian Liu, Jing He, Jue Shi, Zihe Hu, Yanyan Zhou, Zhijian Xie & Yong He, Volume 17, article number 27, (2025)) discloses a 3D printing method for tough hydrogel scaffolds with functional surface structures for tissue regeneration. This method includes: first, 3D printing to fabricate a hydrogel scaffold (P) with the desired structure; then, through salting-out-assisted cyclic mechanical training (T), the scaffold can acquire very high mechanical properties and functional surface structures; finally, the training results are fixed by photocrosslinking treatment (C). The resulting tough gelatin hydrogel, named PTC, has a tensile strength of 6.66 MPa.

[0005] The main technical problems with existing technologies are:

[0006] (1) The existing methods of stretching training are aimed at hydrogels that have only been cured by condensation and photocrosslinking. Their initial structure has many defects (for example, the GelMA molecular chains are randomly oriented and in a random coiled conformation, and the molecular chains are entangled with each other; some chain segments are temporarily and weakly combined through physical actions such as hydrogen bonds and hydrophobic interactions, forming a weak interaction region; there are bubbles inside, etc.), and the initial state of the material is very poor.

[0007] (2) In the existing technical methods, the tensile strain on the hydrogel remains constant. It is effective in the early stage of training, but after several rounds, the internal structure of the hydrogel has adapted to this strain. Subsequent training only maintains this structure and cannot provide further strengthening stimulation, which limits the formation of more physical cross-links and further orientation of the internal molecular chains, and the performance cannot be further improved. Moreover, any macroscopically uniform material has structural inhomogeneity at the micro level. The tensile strain in the initial round of the existing method is very large. Instead of transitioning from low strain to high strain to gently adapt to the internal properties of the material, it will exceed the bearing limit of the local area inside the material and easily cause irreversible damage to the internal structure of the material.

[0008] (3) In the existing technical method, the process ends after the stretching training is completed. Due to the short training time, the already oriented chain segments inside the hydrogel do not have enough time to move to their lowest and most stable positions. The salting-out effect and dehydration cannot be sustained or carried out in depth. Sulfate ions and ammonium ions cannot diffuse and penetrate evenly into all areas inside the sample. This results in problems such as poor thermodynamic relaxation, uneven crosslinking density, sparse crosslinking points, and unstable network structure in the internal structure of the treated sample. Moreover, the effective release of internal stress and the solidification of stable structure after training are ignored. The large amount of residual stress remaining inside the material will cause its mechanical properties to regress or become unstable in subsequent use.

[0009] (4) The tensile strength improved by existing technologies is not high enough, only reaching 6.66MPa and 6.67MPa, which limits the scope of application. Summary of the Invention

[0010] To address the problems existing in the prior art, the present invention provides a method for preparing a high-strength hydrogel, the tough hydrogel (CPTR) prepared by this method having higher tensile strength.

[0011] A method for preparing a high-strength hydrogel includes: centrifuging, condensing, and photocuring a hydrogel precursor solution sequentially; subjecting the photocured hydrogel to progressive cyclic stretching training and immersion in PBS; and finally allowing it to stand in a sulfate solution to obtain the high-strength hydrogel; wherein the stretching training is performed in a sulfate solution; the above cycle consists of multiple rounds of stretching training and immersion in PBS, wherein one or more adjacent rounds of stretching training and immersion in PBS constitute a sub-cycle, and the tensile strain in each sub-cycle is greater than the tensile strain in the previous sub-cycle.

[0012] Compared with existing similar technologies, the method of this invention, through centrifugation of the hydrogel precursor solution, alters the stretching and orientation of internal molecular chains, reconstructs weak interaction regions, and eliminates air bubbles, resulting in a more uniform and dense chain distribution. This eliminates stress concentration points and structural defects in the subsequently cured network. The progressive stretching training process increases the energy barrier height with each increase in tensile strain, expanding the network's deformability and promoting the redistribution and homogenization of internal structural stress. This dynamically improves its load-bearing capacity and plasticity. Subsequent training further disrupts the relatively weak connections formed during previous training, creating stronger and more stable ionic bonds, salt bridges, hydrogen bonds, and hydrophobic stacks, leading to denser physical crosslinking and entanglement between already oriented molecular chains. By placing the hydrogel in a sulfate solution for an extended period after training, the internal structure has sufficient time for thermodynamic relaxation, allowing for further fine-tuning of the oriented molecular chains, forming more and higher-quality interaction sites, eliminating local stress, and creating a more regular and compact bundled structure. Simultaneously, the salting-out effect continues undisturbed, reducing SO42-. 2- and NH4 + Further hydration and uniform diffusion permeation form a more uniform and tightly entangled physical cross-linked network and a larger number of stable salt bridges and ionic bonds.

[0013] In summary, the synergistic effect of the combination of centrifugation, progressive stretching training, and long-term static setting can produce a tough hydrogel with highly ordered molecular chain arrangement. The uniform and dense network structure formed during the process, the large number and stronger inter-chain hydrogen bonds, the continuously improved orientation of molecular chains along the stretching direction, the large number of salt bridges and ionic bonds formed by the target sites provided by sulfate and ammonium ions, and the fewer internal weak interaction points, bubbles and other defects improve the strength and toughness of the hydrogel.

[0014] The hydrogel material obtained by the method of this invention provides unprecedented high strength in the field of high-strength hydrogels. The combination of different processes achieves a synergistic effect, exhibiting an excellent tensile strength of 134.31 MPa, which is 2920 times that of the untreated gelled material.

[0015] Preferably, the centrifuge speed during centrifugation is 500~4000 rpm. More preferably, it is 1000~3000 rpm. Even more preferably, it is 1500~2500 rpm.

[0016] Preferably, the centrifuge time is set to 60-300 s during centrifugation. More preferably, it is 120-240 s. Even more preferably, it is 160-200 s.

[0017] Preferably, the condensation temperature is set to 2~8℃ during the condensation process. More preferably, it is 3~5℃. Even more preferably, it is 4℃.

[0018] Preferably, the condensation time is set to 900~2700s during the condensation process. More preferably, it is 1500~2100s. Even more preferably, it is 1800s.

[0019] Preferably, the wavelength of the light is set to 380 nm to 410 nm during the photocrosslinking process. More preferably, it is 395 nm to 410 nm. Even more preferably, it is 405 nm.

[0020] Preferably, during the photocrosslinking process, the distance between the irradiation lamp and the hydrogel is set to 5-30 mm. More preferably, it is 10-20 mm. Even more preferably, it is 13-17 mm.

[0021] Preferably, the illumination time during the photocrosslinking process is set to 3-15 s. More preferably, it is 5-12 s. Even more preferably, it is 6-10 s.

[0022] Furthermore, during the entire stretching training process, the initial tensile strain of the hydrogel under axial reciprocating stretching in a sulfate (preferably ammonium sulfate) solution (first round of stretching training) is 20%~40%; more preferably 25%~35%. Even more preferably 30%.

[0023] Furthermore, the number of sub-cycles during the entire stretching training process is 2 to 10 sets; more preferably 4 to 6 sets. Even more preferably 4 sets.

[0024] Furthermore, each sub-cycle includes 2 to 10 rounds of stretching training followed by immersion in PBS; more preferably 4 to 6 rounds. Even more preferably 5 rounds.

[0025] Furthermore, during each round of stretching training, the hydrogel is axially stretched 15-30 times in the sulfate solution. More preferably, it is 18-24 times. Even more preferably, it is 21 times.

[0026] Furthermore, during each round of stretching training, the stretching rate of the hydrogel in the sulfate solution (ammonium sulfate solution) is 1~15 mm / min; more preferably 2~9 mm / min. Even more preferably 3 mm / min.

[0027] Furthermore, the increase in tensile strain between adjacent sub-cycles is 1% to 10%. That is, at the strain-increase point during the entire stretching training process, the strain of the hydrogel under axial reciprocating stretching in the sulfate solution increases by 1% to 10%; or, in the current sub-cycle, the tensile strain increases to 1% to 10% of the tensile strain of the previous sub-cycle. More preferably, it is 2% to 5%. Even more preferably, it is 3%.

[0028] Furthermore, during each round of stretching training and immersion in PBS, the hydrogel is immersed in the PBS solution for 20–160 seconds. More preferably, it is 40–90 seconds. Even more preferably, it is 65 seconds.

[0029] Furthermore, throughout the stretching training process, the number of cycles of axial reciprocating stretching of the hydrogel in sulfate solution and immersion in PBS solution is 15 to 25. More preferably, it is 18 to 22 cycles. Even more preferably, it is 20 cycles.

[0030] Furthermore, in each subcycle, the parameters for multiple rounds of stretching training and immersion treatment in PBS were the same.

[0031] Furthermore, during the settling process, the hydrogel is settling in the sulfate solution for 6–48 hours. More preferably, it is 12–36 hours. More preferably, it is 18–30 hours; and even more preferably, it is 24 hours.

[0032] Preferably, the sulfate solution is an ammonium sulfate solution.

[0033] Preferably, the concentration of the sulfate solution is 35-65%; more preferably 42-57%. Even more preferably 52%.

[0034] As a preferred embodiment, the initial tensile strain is 25%~35%; the increase in tensile strain between adjacent sub-cycles is 2%~5%; the number of cycles is 15~25; each sub-cycle includes 4~6 cycles; the hydrogel is soaked in PBS solution for 40~90s; during each round of stretching training, the stretching rate of the hydrogel in sulfate (preferably ammonium sulfate) solution is 2~9mm / min; the hydrogel is left to stand in sulfate solution for 18~30h; and the concentration of the sulfate solution is 42~57%.

[0035] Preferably, the hydrogel includes one or more of gelatin, hyaluronic acid, etc.; more preferably, it is methacrylamide gelatin.

[0036] Preferably, the preparation method of the hydrogel includes, but is not limited to, mold casting, photopolymerization additive manufacturing, and extrusion additive manufacturing. More preferably, the preparation method of the hydrogel is mold casting.

[0037] Preferably, the PBS solution is a mixture of Na₂HPO₄, KH₂PO₄, NaCl, and KCl. The pH of the PBS solution is 6-8.

[0038] Preferably, the temperature at which the hydrogel is axially stretched in ammonium sulfate solution, the immersion temperature in PBS solution, and the standing temperature in ammonium sulfate solution are each independently selected from 22 to 28°C. More preferably, it is 25°C.

[0039] The present invention also provides a high-strength hydrogel, which is prepared by any of the preparation methods described above.

[0040] The present invention provides a method for preparing a high-strength hydrogel, comprising:

[0041] The hydrogel solution was centrifuged to create an ordered and dense initial template, and then condensed in a refrigerator at 2-8°C. After condensation, it was photocured with a UV lamp. The hydrogel was then subjected to progressive cyclic stretching training in a sulfate solution and soaked in PBS, which was repeated to further induce polymer chain orientation. Finally, it was left to stand in an ammonium sulfate solution for a long time to provide a static, undisturbed opportunity for deep cross-linking inside the sample and lock in the training results.

[0042] In the above preparation method, the entire loading process is similar to human fitness exercises. Centrifugation is equivalent to warm-up exercises, progressive overload cyclic stretching training is equivalent to progressively increasing load sets during strength training, and prolonged immersion in sulfate solution is equivalent to the supercompensation effect after anaerobic exercise. During centrifugation, the hydrogel solution undergoes chain stretching and orientation changes, weak interaction regions are disrupted and reconstructed, and air bubbles are eliminated. During progressive cyclic stretching training, structural evolution, optimization processes, and network orientation are continuously triggered, maximizing the exposure of potential reaction sites. During prolonged immersion, thermodynamic relaxation is promoted, the structure is deeply optimized, the salting-out effect is fully and continuously carried out, and the crosslinking density becomes more uniform.

[0043] This invention can produce hydrogel fibers. During the production process, the fibers can be directly cured in a transparent silicone tube with an inner diameter of 0.1~2.0 mm, more preferably 0.5~1.1 mm. Alternatively, they can be cured in a mold with a specific structure to obtain a hydrogel product or hydrogel fiber with a corresponding structure.

[0044] As a preferred embodiment, a method for preparing a high-strength hydrogel includes the following steps:

[0045] Step 1: Place the prepared hydrogel precursor solution into a centrifuge tube, and then place the centrifuge tube in a centrifuge for centrifugation. Set the centrifuge speed to 500~4000 rpm and the time to 60~300s.

[0046] Step 2: After pouring the hydrogel precursor solution prepared in Step 1 into the pre-prepared mold, place it in an environment of 2~8℃ to condense, and set the condensation time to 900~2700s;

[0047] Step 3: Photocrosslinking and curing of the hydrogel prepared in Step 2. The wavelength of the light is 380~410nm, the distance between the irradiation lamp and the hydrogel is 5~30mm, and the irradiation time is 3~15s.

[0048] Step 4: Add the ammonium sulfate solution and PBS solution to the two tanks used for hydrogel training, respectively;

[0049] Step 5: Place the hydrogel prepared in Step 3 into an ammonium sulfate solution and perform axial reciprocating stretching 15-30 times, with a tensile strain of 20%-40%;

[0050] Step 6: Immerse the hydrogel prepared in Step 5 in PBS solution for 20-160 seconds;

[0051] Step 7: Repeat steps 5 and 6 5 times;

[0052] Step 8: Place the hydrogel prepared in Step 7 into an ammonium sulfate solution and perform axial reciprocating stretching 15-30 times, with a tensile strain of 21%-50%;

[0053] Step 9: Immerse the hydrogel prepared in step 8 in PBS solution for 20-160 seconds;

[0054] Step 10: Repeat steps 8 and 9 5 times;

[0055] Step 11: Place the hydrogel prepared in Step 10 into an ammonium sulfate solution and perform axial reciprocating stretching 15-30 times, with a tensile strain of 22%-60%;

[0056] Step 12: Immerse the hydrogel prepared in Step 11 in PBS solution for 20-160 seconds;

[0057] Step Thirteen: Repeat Step Eleven and Step Twelve five times;

[0058] Step Fourteen: Place the hydrogel prepared in Step Thirteen into an ammonium sulfate solution and perform axial reciprocating stretching 15-30 times, with a tensile strain of 23%-70%;

[0059] Step 15: Immerse the hydrogel prepared in Step 14 in PBS solution for 20-160 seconds;

[0060] Step 16: Repeat steps 14 and 15 five times;

[0061] Step 17: Place the hydrogel prepared in Step 16 in an ammonium sulfate solution and let it stand for 6-48 hours to obtain the tough hydrogel.

[0062] Furthermore, the tensile strain in steps five, eight, eleven, and fourteen gradually increases. That is, the tensile strain in step five is less than the tensile strain in step eight, the tensile strain in step eight is less than the tensile strain in step eleven, and the tensile strain in step eleven is less than the tensile strain in step fourteen.

[0063] This invention provides a method for preparing high-strength hydrogels, which breaks through the maximum tensile strength of existing technologies for preparing strong and tough hydrogels, and can also be used to create hydrogel fibers and networks, which has great medical, scientific research and commercial value.

[0064] The method for preparing high-strength hydrogels provided by this invention is characterized by high strength, high efficiency, low cost, and ease of operation, and is applicable to a variety of hydrogels. The tensile strength of the hydrogels obtained by this method far exceeds the limits of existing similar technologies. The tensile strength of CPTR reaches 134.31 MPa, which is 2920 times that of untreated gel (initial hydrogel) and 20 times that of existing similar technologies.

[0065] The high-strength hydrogel, hydrogel fibers, and networks obtained by this invention offer broad application prospects for regenerative medicine, tissue engineering, and other fields.

[0066] The preparation method of this invention involves centrifugation, condensation, photocrosslinking, progressive stretching training, and prolonged static immersion in ammonium sulfate solution to prepare a high-strength hydrogel with numerous salt bridges and ionic bonds formed by target sites provided by sulfate and ammonium ions. This hydrogel exhibits a uniform, dense, and stable network structure with more crosslinking points, a greater number of strong hydrogen bonds, fewer internal weak interaction points, and fewer defects such as bubbles. The hydrogel fibers and hydrogel networks prepared by this method offer extremely broad prospects for regenerative medicine, tissue engineering, and other fields.

[0067] The method for preparing high-strength hydrogels of the present invention is convenient to operate, low in cost, highly efficient, and produces high strength, providing a new approach for the application of hydrogels in high-strength scenarios in regenerative medicine and tissue engineering.

[0068] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0069] (1) The high-strength hydrogel preparation method of the present invention is a supplementary method to the existing tough hydrogel preparation method, which expands the existing tough hydrogel manufacturing method. It is simple to operate, highly efficient, and has great application potential in many fields such as regenerative medicine and tissue engineering.

[0070] (2) The method for preparing high-strength hydrogel of the present invention can prepare a tough hydrogel with highly ordered molecular chain arrangement. The uniform and dense network structure formed in the process, a large number of stronger inter-chain hydrogen bonds, continuously improved orientation of molecular chains along the stretching direction, and a large number of salt bridges and ionic bonds formed by target points provided by sulfate ions and ammonium ions, and fewer internal weak interaction points, bubbles and other defects, improve the strength and toughness of the hydrogel.

[0071] (3) In the centrifugation process of the high-strength hydrogel preparation method of the present invention, the centrifugal force counteracts the Brownian motion of the chain segments, overcomes the conformational entropy of the chain, and forces the randomly coiled chain clusters to stretch along the direction of the centrifugal force, gradually straightening the randomly coiled chains. The chains extend and untangle along the direction of the centrifugal force, and the center of mass of all molecular chains is subjected to the same force. Therefore, not only are individual chains straightened, but all adjacent chains also tend to be arranged in parallel along the direction of the force field, forming a partially ordered structure. Simultaneously, a flow-induced orientation effect occurs. During centrifugation, the solution itself undergoes slow radial flow or shearing due to centrifugal force. Randomly coiled chains, captured by the shear flow field, begin to rotate, becoming elongated and alternately stretched and compressed along the streamline direction. As the shear rate increases, the chains do not have enough time to complete the full rotation, maintaining their orientation along the flow field direction. The long axis of the chain aligns with the flow field direction to reduce flow resistance. Molecular chains will orient and align along the flow field direction in the shear flow field. Centrifugal force and the induced flow field resist thermal motion, jointly causing the molecular chains to stretch and align radially. At the same time, the molecular chains in the solution are not completely uniformly dispersed. Some chain segments temporarily and weakly bind through physical interactions such as hydrogen bonds, hydrophobic interactions, and ionic bonds, forming some local, unstable entanglement points, constituting weak interaction regions. This leads to local unevenness in solution concentration and the formation of defect points in subsequent cross-linking. When the centrifugal force exceeds the binding energy of the weak interaction, it will force relative slippage between molecular chains, breaking up loose chain clusters and improving the density and uniformity of topological entanglement between chains. The distribution of the chains is more uniform and dense; and in the centrifugal force field, the net force on the particles in the fluid is proportional to the density difference. Since the density of the bubbles is much smaller than that of the solution, the net force on the bubbles is opposite to the centrifugal force. That is, the component with a density much lower than that of the solvent will be subjected to centripetal force. The bubbles will move and gather towards the central axis of the centrifugal force field and eventually disappear at the liquid surface, thereby eliminating stress concentration points and structural defects in the subsequent solidification network.

[0072] (4) The progressive stretching training process in the preparation method of the high-strength hydrogel of the present invention will enable the system to overcome the energy barrier each time the tensile strain is increased, and jump from a relatively metastable state to a more stable state. The energy barrier height is increased, which forces the system to explore a better and more stable configuration in the energy landscape, ensuring that further strengthening stimulation can be provided when the training load increases. After each small strain increment is applied, the stress in the internal structure of the hydrogel is relaxed and redistributed. The stress in the high stress area is transferred to the low stress area, making the stress distribution tend to be uniform, avoiding destructive stress concentration, and maintaining the integrity of the structure throughout the training process. Its load-bearing capacity and plasticity are dynamically improved. The subsequent training continues to destroy the relatively weak connections formed in the previous training and promotes the formation of stronger and more stable ionic bonds, hydrogen bonds and hydrophobic stacks in a more stretched state. At the same time, each cycle of loading will cause weak and irreversible damage to the material. When the accumulated damage reaches a critical value, the material is destroyed. With fixed strain training, the remaining network connection points can no longer be effectively destroyed in a certain round, and the training effect enters a plateau period. In progressive training, increasing the strain amplitude ensures that even in the later stages of training, each cycle effectively filters and destroys the weakest links in the current network, forcing the network to continuously evolve towards a more stable configuration. The degree of stretching of molecular chains can be described by the elongation ratio (stretched length / original length). A higher elongation ratio means that the orientation of molecular chains along the stretching direction continues to increase, thereby expanding the deformation capability of the network and promoting the formation of denser physical crosslinks and entanglements between already oriented molecular chains, resulting in stronger bonding and improved mechanical properties along the stretching direction. Moreover, under greater tensile strain, hydrophobic segments and polar functional groups that were originally encased within the chain clusters are exposed, which allows ammonium sulfate ions (SO42-) to be released. 2- NH4 + This provides more targets for forming salt bridges and ionic bonds, further increasing the density of physical cross-linking. In the initial low-strain stage, the most mobile and rearranged segments begin to adjust first. As the strain gradually increases, the less mobile segments begin to participate in reconstruction. This orderly, phased process is conducive to efficient self-optimization.

[0073] (5) The long-term static process in the preparation method of the high-strength hydrogel of the present invention allows the system sufficient time for thermodynamic relaxation without external interference. The molecular chains that have already been initially oriented can be fine-tuned to eliminate local stress and form a more regular and compact bundle structure. The chain segments can find more and better interaction sites through tiny movements, thereby allowing the entire network structure to transition to a more stable state and the structure to be more perfect. Moreover, in the previous training process, the time of the sample in the ammonium sulfate solution is intermittent, and the salting-out effect is frequently interrupted. With long-term continuous immersion, the salting-out effect can continue without interference. 2-and NH4 + The strong hydration capacity continuously competes for water molecules in the network, reducing the solubility of polymer chains in the solvent. This leads to further dehydration of the polymer chains, enhancing interchain hydrophobic interactions and hydrogen bonding, reducing the interchain spacing, and causing entanglement. This induces the formation of numerous additional, robust physical cross-linking points, resulting in a denser physical cross-linked network. Furthermore, the orientation and reinforcement caused by mechanical training are not entirely uniform within the sample: regions with high strain may have denser cross-linking, while regions with low strain may have relatively sparser cross-linking. Prolonged static immersion causes SO42- to... 2- and NH4 + Uniform diffusion and penetration, along with sufficient and uniform salting-out reinforcement, leads to an increased and more evenly distributed overall crosslinking density, eliminating localized weak points and comprehensively improving the material's macroscopic mechanical properties. Furthermore, under the tension state created by mechanical training, SO4... 2- and NH4 + It forms numerous and stable salt bridges and ionic bonds with functional groups in the molecular chain, further promoting physical cross-linking.

[0074] (6) The method for preparing high-strength hydrogel of the present invention realizes the synergistic effect of different process combinations such as centrifugation, progressive stretching training and long-term static placement in ammonium sulfate solution.

[0075] (7) The high-strength hydrogel of the present invention has excellent mechanical properties (tensile strength up to 134.31 MPa, which is 2920 times higher than the initial hydrogel and 20 times higher than the existing similar technology).

[0076] (8) The high-strength hydrogel preparation method of the present invention can prepare hydrogel fibers and networks. The prepared network can support an iron ball that is 367 times heavier than itself and 79 times larger than itself in diameter. It can withstand the impact of a bullet with a speed of 15.2 m / s and an average impact force of 2.964 N, demonstrating its excellent mechanical properties and providing new ideas for tissue engineering, regenerative medicine and other fields. Attached Figure Description

[0077] Figure 1 In the diagram: A is a comparison of the mechanical properties of the optimal performance group among different process combinations; B is a morphology diagram of the high-strength hydrogel prepared by the method of this invention; C is a diagram of the high-strength hydrogel under torsion and blade cutting conditions; D is a diagram with a cross-sectional area of ​​only 0.306 mm². 2 A diagram showing the state of the high-strength hydrogel when it withstands a 1.58kg drinking water bottle;

[0078] Figure 2 X-ray diffraction characterization results of strong and tough hydrogels prepared under different process combinations;

[0079] Figure 3The results of differential thermogravimetric analysis characterization of tough hydrogels prepared under different process combinations are shown in the figure.

[0080] Figure 4 Thermogravimetric analysis (TGA) characterization results of tough hydrogels prepared under different process combinations are shown in the figure.

[0081] Figure 5 Figure 1 shows the differential scanning calorimetry characterization results of strong and tough hydrogels prepared under different process combinations.

[0082] Figure 6 Scanning electron microscopy characterization results of strong and tough hydrogels prepared under different process combinations;

[0083] Figure 7 Figure A shows the small-angle X-ray scattering characterization results of the tough hydrogels prepared under different process combinations, and Figure B shows the wide-angle X-ray scattering characterization results of the tough hydrogels prepared under different process combinations.

[0084] Figure 8 Fourier transform infrared spectroscopy characterization results of strong and tough hydrogels prepared under different process combinations;

[0085] Figure 9 Raman spectral characterization results of strong and tough hydrogels prepared under different process combinations;

[0086] Figure 10 In the diagram: A shows a comparison of the mechanical properties of high-strength hydrogels prepared under different tensile strain parameters in the PT combination; B shows a comparison of the mechanical properties of high-strength hydrogels prepared under different tensile strain parameters in the PTR-12h combination; C shows a comparison of the mechanical properties of high-strength hydrogels prepared under different tensile strain parameters in the PTR-24h combination; D shows a comparison of the mechanical properties of high-strength hydrogels prepared under different tensile strain parameters in the PTR-36h combination.

[0087] Figure 11 In the diagram: A shows a comparison of the mechanical properties of high-strength hydrogels prepared under different tensile strain parameters in the CPT combination; B shows a comparison of the mechanical properties of high-strength hydrogels prepared under different tensile strain parameters in the CPTR-12h combination; C shows a comparison of the mechanical properties of high-strength hydrogels prepared under different tensile strain parameters in the CPTR-24h combination; D shows a comparison of the mechanical properties of tough hydrogels prepared under different tensile strain parameters in the CPTR-36h combination.

[0088] Figure 12 In the middle: A, B, C, D, E, and F are the scanning electron microscopy characterization results of the high-strength hydrogels before and after soaking in EGDMA and after soaking in PBS solution for 1 day, 3 days, 5 days, and 7 days, respectively;

[0089] Figure 13 The graph shows the changes in volume, mass, and compressive modulus of the high-strength hydrogel before and after soaking in EGDMA and after soaking in PBS solution for different numbers of days (BS: before soaking in EGDMA; AS-0: after soaking in EGDMA; AS-x: after soaking in PBS solution for x days).

[0090] Figure 14 In the diagram: A shows a single-strand hydrogel fiber; B shows the mechanical properties of a single-strand hydrogel fiber tested on a universal testing machine; C and D show the preparation of nine-strand hydrogel fibers; E shows a comparison of the mechanical properties of different strands of hydrogel fibers (PBS-1: single-strand hydrogel fiber treated only with PBS; AS-x: x-strand hydrogel fibers treated with ammonium sulfate solution); F shows a strong and tough hydrogel network; G shows the mechanical properties of the hydrogel network tested on a universal testing machine.

[0091] Figure 15 In the diagram: A shows the comparison of mechanical properties of hydrogel networks with different diameters; B shows the comparison of mechanical properties of hydrogel networks with different equidistant pore spacings; C shows the comparison of mechanical properties of hydrogel networks with different pore spacings.

[0092] Figure 16 Image A shows a hydrogel network supporting a steel ball; image B shows a comparison of the diameter and mass of the steel ball and the hydrogel network; image C shows a high-speed camera image of a bullet before it hits the hydrogel network; image D shows a high-speed camera image of a bullet hitting the hydrogel network; image E shows a high-speed camera image of a bullet after it hits the hydrogel network. Detailed Implementation

[0093] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. Unless otherwise specified, the equipment and reagents used in the embodiments and experimental examples are commercially available. The specific embodiments described herein are for illustrative purposes only and are not intended to limit the invention.

[0094] Example 1

[0095] A method for preparing a high-strength hydrogel includes the following steps:

[0096] 1. Add 2g of GelMA hydrogel and 0.08g of LAP to a conical centrifuge tube (50ML). Pour 40ml of phosphate buffered saline (PBS) solution (pH 7.4) into the tube. Then place the centrifuge tube in a constant temperature water bath at 55℃ until completely dissolved to obtain the hydrogel precursor solution.

[0097] 2. Place the centrifuge tubes in the centrifuge, balance them, and then centrifuge them. Set the centrifuge speed to 2000 rpm and the centrifugation time to 180 s.

[0098] 3. Slowly pour PDMS (polydimethylsiloxane) (containing PDMS monomer and corresponding curing agent, the monomer and curing agent are mixed in a ratio of 10:1 and treated with vacuum defoamer) into the cleaned mold, place it in an oven at 80℃ and let it stand for 2 hours to prepare the PDMS mold, and then drop an appropriate amount of the prepared hydrogel precursor solution into the PDMS mold.

[0099] 4. Place the mold in a 4℃ environment and let it stand for 1800 seconds. Then, expose it to light with a wavelength of 405nm for 8 seconds to perform cross-linking and curing. The light source should be 15mm away from the mold. Remove the cured hydrogel to obtain the initial hydrogel (GelMA).

[0100] 5. Make two rectangular open-top tanks using acrylic material, and add appropriate amounts of (NH4)2SO4 (w / v 50%) solution and PBS solution (pH 7.4) to each.

[0101] 6. Completely immerse the cured hydrogel (initial hydrogel) in a (NH4)2SO4 (w / v 50%) solution and axially reciprocate it 21 times at a speed of 3 mm / min, with a tensile strain of 30% each time. Then immediately immerse it in PBS solution for 65 s. This constitutes one cycle. Repeat this cycle for 5 rounds.

[0102] 7. Completely immerse the hydrogel treated in step 6 in a (NH4)2SO4 (w / v 50%) solution and axially reciprocate it 21 times at a speed of 3 mm / min, with a tensile strain of 33%. Then immediately immerse it in PBS solution for 65 s. This constitutes one cycle. Repeat this cycle for 5 rounds.

[0103] 8. Completely immerse the hydrogel treated in step 7 in a (NH4)2SO4 (w / v 50%) solution and axially reciprocate it 21 times at a speed of 3 mm / min, with a tensile strain of 36%. Then immediately immerse it in PBS solution for 65 s. This constitutes one cycle. Repeat this cycle for 5 rounds.

[0104] 9. Completely immerse the hydrogel treated in step 8 in a (NH4)2SO4 (w / v 50%) solution and axially reciprocate it 21 times at a speed of 3 mm / min, with a tensile strain of 39%. Then immediately immerse it in PBS solution for 65 s. This constitutes one cycle. Repeat this cycle for 5 rounds.

[0105] 10. Completely immerse the hydrogel treated in step 9 in a (NH4)2SO4 (w / v 50%) solution and let it stand for 24 hours to obtain the strong and tough hydrogel obtained by the method of the present invention.

[0106] Simultaneously, the following samples were prepared using the methods described above:

[0107] PT: Hydrogel product without centrifugation treatment, only subjected to progressive stretching training: obtained according to steps (1), (3)~(9);

[0108] CPT: Hydrogel obtained by centrifugation and progressive stretching training without long-term static treatment: obtained according to steps (1) to (9);

[0109] PTR: Hydrogel obtained by progressive stretching training and long-term static treatment without centrifugation: obtained according to steps (1), (3) to (10);

[0110] CPTR: Hydrogel obtained by centrifugation + progressive stretching training + long-term static treatment: obtained according to steps (1) to (10).

[0111] Performance testing and characterization:

[0112] Using a universal testing machine and the same tensile parameters, the mechanical properties of hydrogels that had undergone only progressive tensile training, hydrogels that had undergone centrifugation and progressive tensile training, hydrogels that had undergone progressive tensile training and long-term static treatment, and hydrogels that had undergone centrifugation, progressive tensile training, and long-term static treatment were tested. The reference standard code was GB / T13022-1991, the type was set to tensile, the tensile rate was set to 5 mm / min, and the control method was set to displacement mode (see the tensile process of the device). Figure 14 (See schematic diagram B in the diagram), the test results are as follows: Figure 1 As shown in Figure A. From Figure 1 As can be seen from Figure A, the tensile strength (stress) and elongation at break (strain) of the tough hydrogels treated with different combinations of processes differ significantly. Figure 1 As can be seen from B, the tough hydrogel prepared in this embodiment has obvious reinforcement marks; Figure 1 In the middle, C represents the state of the strong and tough hydrogel under torsion and blade cutting. Figure 1 In this embodiment, the cross-sectional area D is only 0.306 mm². 2 Diagram showing the condition of a handle made of strong hydrogel that can withstand 1.58 kg of drinking water.

[0113] X-ray diffraction (XRD) characterization: Instrument model: Bruker D8 Advance diffractometer (Cu-Karadiation 1.540598A). Test conditions were set as follows: 2θ angle 5–90°; step size 0.02°; time / step 0.1 s. Optical path conditions were set as follows: main Soler slit 4.1° / 4.0°; air scattering screen mode: automatic; scattering slit 0.5°. Voltage: 40 kV; current: 40 mA; detector: LYNXEYEXE-T. Figure 2 X-ray diffraction (XRD) characterization results of the tough hydrogels prepared under different process combinations are shown. The results reveal variations in the intensity and position of the amorphous halo around 20°, indicating changes in network density and uniformity. Higher peak intensities indicate tighter molecular chain arrangement, a more ordered network, and better network uniformity. Clearly, the CPTR peak has the highest intensity at 2695.

[0114] Thermogravimetric analysis (TG) characterization: The instrument was a Mettler Toledo simultaneous thermal analyzer TGA / DSC 3+. Experimental conditions were: under nitrogen atmosphere, initial temperature 30℃, heated to 1000℃ at a rate of 10℃ / min. TG characterization reveals the extent to which the processing technology increased the final thermal decomposition temperature of the material. A sample with better mechanical properties and a more dense and stable network structure has stronger intermolecular forces, requiring higher temperatures to break these chemical bonds and decompose and vaporize. Therefore, it will exhibit a higher decomposition temperature and less weight loss on the TGA curve. Figure 3 , Figure 4 The figures show the differential thermogravimetric analysis (TGA) and thermogravimetric analysis (TGA) characterization results of the tough hydrogels prepared under different process combinations. The figures show that CPTR exhibits the highest initial decomposition temperature and maximum weight loss rate temperature, at 275.2℃ and 299.2℃, respectively.

[0115] Differential scanning calorimetry (DSC) characterization: The instrument used was a Mettler Toledo DSC 3 differential scanning calorimeter. Experimental conditions were: nitrogen atmosphere, nitrogen flow rate set to 50 mL / min. The sample was first held at 10 °C for 3 min, then heated to 100 °C at a rate of 5 °C / min, held at 100 °C for 3 min, and then cooled to 10 °C at a rate of 5 °C / min. Differential scanning calorimetry is an important tool for studying the thermal stability of materials. It reveals phase transitions occurring within the material by accurately measuring the heat change of the sample during heating and cooling. A sample with better mechanical properties has a more stable and ordered internal network structure, and therefore will exhibit a higher phase transition temperature and a larger phase transition enthalpy on the DSC curve. Figure 5The figure shows the differential scanning calorimetry (DSC) characterization results of the tough hydrogels prepared under different process combinations. As can be seen from the figure, CPTR exhibits the highest melting temperature, melting entropy, and peak depth, at 72.17℃, 2.134℃, and 1.325℃, respectively.

[0116] Scanning electron microscopy (SEM) characterization: Instrument model: Zeiss GeminiSEM 300. Experimental parameters: voltage 3kV, aperture set to 60µm, probe: SE2. A Lebo sputtering apparatus was used, with parameters set as follows: vacuum 6pa, sputtering current 30mA, sputtering time 25s. A sample with good mechanical properties will show a denser, more uniform, and smaller pore size network structure in its lyophilized SEM image. Figure 6 The scanning electron microscope (SEM) characterization results of the tough hydrogels prepared under different process combinations are shown in the figure. As can be seen from the figure, CPTR is the best in terms of pore size, network wall thickness and density, structural uniformity, and defect situation.

[0117] Small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS) characterization: Instrument model: XENOCSXEUSS 3.0* small-angle X-ray scatterer. Experimental parameters were set as follows: voltage 70 kV; current 3.5 mA; power 250 W; test time 600 s; light source: copper target. Detector model: Decriss EIGER2 Si 1M, using a point light source, detection wavelength set to 0.154 nm, pixel setting to 75, sample chamber maintained under vacuum, no carrier used during sample detection. During SAXS characterization, the distance between the SD detector and the sample was 1500 mm; during WAXS characterization, the distance between the SD detector and the sample was 42.5 nm. Figure 7 Figure A shows the small-angle X-ray scattering (SAXS) characterization results of the tough hydrogels prepared under different process combinations, and Figure B shows the wide-angle X-ray scattering (WAXS) characterization results of the tough hydrogels prepared under different process combinations. According to the SAXS characterization results, the CPTR has the best global ellipticity and surface fractal dimension, which are 1.1316 and 2.5624, respectively. According to the WAXS characterization results, the CPTR has the best peak value, which is 1857.54.

[0118] Fourier transform infrared (FTIR) characterization: Instrument model: NICOLET iS50FT-IR (Thermo Scientific). Experimental parameters were set as follows: resolution: 4 cm⁻¹ -1 The number of scans was 32, and the scan range was 4000 cm⁻¹. -1 ~400cm -1In FTIR infrared spectroscopy, the stronger and more numerous the hydrogen bonds, the more pronounced the redshift and broadening phenomena become, with the redshift being the most significant factor. The amide A band, as a direct probe of hydrogen bond strength, primarily exhibits NH stretching vibrations, which overlap with OH stretching vibrations. The focus is on peak position and shape. Figure 8 Fourier transform infrared (FTIR) spectra of the tough hydrogels prepared under different process combinations are shown in the figures. As can be seen from the figures, the CPTR exhibits the most significant redshift at a wavelength of 3195 cm⁻¹. -1 .

[0119] Raman spectroscopy (RAMAN) characterization: A Renishaw multichannel Raman spectrometer was used. Experimental parameters were set as follows: exposure time 1.000 s; laser power 1000%; excitation wavelength 200 nm–3800 nm. Raman characterization reflects changes in the secondary structure of proteins and the microenvironment of specific amino acid side chains. Figure 9 The Raman spectra of the tough hydrogels prepared under different process combinations are shown in the figure. The peak at 975 cm⁻¹ in the figure is from the SO bond vibration of sulfate ions. The denser and more homogeneous the internal structure of the hydrogel, the better the mechanical properties, and the stronger the peak at 975 cm⁻¹. Obviously, CPTR has the highest intensity, which is 92386.2.

[0120] Swelling invariance test: The sample prepared in this experiment was immersed in ethylene glycol dimethacrylate (EGDMA) for 5 minutes, and then immersed in PBS (pH 7.4). Its volume, mass and compressive modulus were measured after 1 day, 3 days, 5 days and 7 days. Figure 12 The scanning electron microscopy characterization results of the high-strength hydrogels before and after soaking in EGDMA and after soaking in PBS solution for different numbers of days are shown. Figure 12 In the image: A shows the scanning electron microscopy (SEM) characterization results of the high-strength hydrogel before soaking in EGDMA; B shows the SEM characterization results of the high-strength hydrogel after soaking in EGDMA; C shows the SEM characterization results of the high-strength hydrogel after soaking in PBS solution for 1 day; D shows the SEM characterization results of the high-strength hydrogel after soaking in PBS solution for 3 days; E shows the SEM characterization results of the high-strength hydrogel after soaking in PBS solution for 5 days; F shows the SEM characterization results of the high-strength hydrogel after soaking in PBS solution for 7 days. Figure 13In the graph: A shows the changes in volume and mass of the strong hydrogel before and after soaking in EGDMA and after soaking in PBS solution for different numbers of days; B shows the changes in compressive modulus of the high-strength hydrogel before and after soaking in EGDMA and after soaking in PBS solution for different numbers of days; (BS: before soaking in EGDMA; AS-0: after soaking in EGDMA; AS-x: soaked in PBS for x days, where x is 1, 3, 5, or 7). As can be seen from the graphs, there are no significant changes in volume, mass, or compressive modulus, which can be considered as its swelling invariance.

[0121] Example 2: Effects of different stretching parameters on high-strength hydrogels under conditions of no centrifugation + stretching + no prolonged static setting.

[0122] High-strength hydrogels were prepared according to the method in Example 1, with the difference that centrifugation was not performed, and after stretching training, they were not placed in ammonium sulfate solution for settling. The initial hydrogels were stretched using different stretching parameters (20% strain stretching (A1B1C1), 30% strain stretching (A1B2C1), 40% strain stretching (A1B3C1), initial 30% strain followed by a 3% increase every 5 rounds (A1B4C1), and initial 30% strain followed by a 10% increase every 5 rounds (A1B5C1), respectively), resulting in five different high-strength hydrogels. The mechanical properties of the five different high-strength hydrogels were tested, and the results are shown in [Figure 1]. Figure 10 A. Figure 10 Figure A shows a comparison of the mechanical properties of five different high-strength hydrogels. Figure 10 As shown in Figure A, when the tensile strain remains constant, the high-strength hydrogel with a tensile strain of 30% exhibits the best mechanical properties. However, during progressive stretching training, the high-strength hydrogel with an initial strain of 30% followed by a 3% increase in strain every 5 rounds demonstrates better mechanical properties than the high-strength hydrogel with an initial strain of 30% followed by a 10% increase in strain every 5 rounds. Therefore, an initial strain of 30% followed by a 3% increase in strain every 5 rounds is selected as the optimal stretching training parameter for GelMA hydrogel.

[0123] Example 3: Effects of different stretching parameters on high-strength hydrogels under conditions of no centrifugation + stretching + long standing time of 12 hours.

[0124] High-strength hydrogels were prepared according to the method of Example 1, except that centrifugation was not performed, and after the stretching training (according to the stretching conditions in Example 2), the hydrogels were placed in ammonium sulfate solution and allowed to stand for 12 hours. The initial hydrogels were then subjected to stretching training using different stretching parameters (stretching parameters of 20% strain, 30% strain, 40% strain, initial 30% strain followed by an increase of 3% strain every 5 rounds, and initial 30% strain followed by an increase of 10% strain every 5 rounds), and five different high-strength hydrogels were prepared (corresponding to: A1B1C2, A1B2C2, A1B3C2, A1B4C2, and A1B5C2, respectively). Figure 10 Figure B is a comparison chart of the mechanical properties of five different high-strength hydrogels.

[0125] Example 4: Effects of different stretching parameters on high-strength hydrogels under conditions of no centrifugation + stretching + long standing time of 24 hours.

[0126] High-strength hydrogels were prepared according to the method of Example 1, except that centrifugation was not performed, and after the stretching training (according to the stretching conditions in Example 2), the hydrogels were placed in ammonium sulfate solution and allowed to stand for 24 hours. The initial hydrogels were then subjected to stretching training using different stretching parameters (20% strain stretching, 30% strain stretching, 40% strain stretching, initial 30% strain followed by an increase of 3% strain every 5 rounds, and initial 30% strain followed by an increase of 10% strain every 5 rounds), and five different tough hydrogels were prepared (corresponding to: A1B1C3, A1B2C3, A1B3C3, A1B4C3, and A1B5C3, respectively). Figure 10 Figure C is a comparison chart of the mechanical properties of five different high-strength hydrogels. From... Figure 10 As can be seen from Figure C, with the extension of the standing time in the ammonium sulfate solution, the stress and strain of the high-strength hydrogel obtained by initially increasing the strain by 3% every 5 rounds from 30% increase both steadily increase to over 65 MPa and over 700%, respectively. However, the stress increase of the hydrogel obtained by stretching with a strain of 30% is slower, reaching only about 30 MPa.

[0127] Example 5: Effects of different stretching parameters on high-strength hydrogels under conditions of no centrifugation + stretching + long standing time of 36 hours.

[0128] High-strength hydrogels were prepared according to the method of Example 1, except that centrifugation was not performed, and after the stretching training (according to the stretching conditions in Example 2), the hydrogels were placed in ammonium sulfate solution and allowed to stand for 36 hours. The initial hydrogels (corresponding to A1B1C4, A1B2C4, A1B3C4, A1B4C4, and A1B5C4, respectively) were stretched using different stretching parameters (20% strain stretching, 30% strain stretching, 40% strain stretching, initial 30% strain followed by an increase of 3% strain every 5 rounds, and initial 30% strain followed by an increase of 10% strain every 5 rounds). Five different high-strength hydrogels were then prepared. Figure 10 Figure D is a comparison chart of the mechanical properties of five different high-strength hydrogels. Figure 10 As can be seen from D, a longer settling time does not further improve the toughness of the hydrogel, and may even reduce it.

[0129] comprehensive Figure 10 For ingredients A through D, the optimal settling time is approximately 24 hours.

[0130] Example 6: Effects of different tensile parameters on high-strength hydrogels under centrifugation + stretching + no prolonged static conditions.

[0131] High-strength hydrogels were prepared according to the method in Example 1, except that after the stretching training, the hydrogels were not placed in ammonium sulfate solution to stand, and different stretching parameters (stretching parameters of 20% strain stretching, 30% strain stretching, 40% strain stretching, initial 30% strain followed by an increase of 3% strain every 5 rounds, and initial 30% strain followed by an increase of 10% strain every 5 rounds) were used to stretch the initial hydrogels, and five different high-strength hydrogels (corresponding to A2B1C1, A2B2C1, A2B3C1, A2B4C1, and A2B5C1, respectively) were prepared. Figure 11 Figure A shows a comparison of the mechanical properties of five different high-strength hydrogels.

[0132] Example 7: Effects of different tensile parameters on high-strength hydrogels under conditions of centrifugation, stretching, and prolonged standing for 12 hours.

[0133] High-strength hydrogels were prepared according to the method in Example 1, except that after the stretching training, the hydrogels were placed in ammonium sulfate solution and left to stand for 12 hours. The initial hydrogels were then subjected to stretching training using different stretching parameters (stretching parameters of 20% strain, 30% strain, 40% strain, initial 30% strain followed by an increase of 3% strain every 5 rounds, and initial 30% strain followed by an increase of 10% strain every 5 rounds). Five different high-strength hydrogels were then prepared (corresponding to A2B1C2, A2B2C2, A2B3C2, A2B4C2, and A2B5C2, respectively). Figure 11Figure B is a comparison chart of the mechanical properties of five different high-strength hydrogels.

[0134] Example 8: Effects of different tensile parameters on high-strength hydrogels under centrifugation, stretching, and prolonged standing time of 24 hours.

[0135] High-strength hydrogels were prepared according to the method in Example 1, except that different tensile parameters were used to stretch the initial hydrogels (20% strain stretching, 30% strain stretching, 40% strain stretching, initial 30% strain followed by an increase of 3% strain every 5 rounds, and initial 30% strain followed by an increase of 10% strain every 5 rounds) to prepare five different high-strength hydrogels (corresponding to A2B1C3, A2B2C3, A2B3C3, A2B4C3, and A2B5C3, respectively). Figure 11 The graph in section C is a comparison of the mechanical properties of five different high-strength hydrogels.

[0136] Example 9: Effects of different tensile parameters on high-strength hydrogels under centrifugation, stretching, and prolonged standing time of 36 hours.

[0137] High-strength hydrogels were prepared according to the method in Example 1, except that after the stretching training, the hydrogels were placed in ammonium sulfate solution and left to stand for 36 hours. The initial hydrogels were then subjected to stretching training using different stretching parameters (20% strain stretching, 30% strain stretching, 40% strain stretching, initial 30% strain followed by an increase of 3% strain every 5 rounds, and initial 30% strain followed by an increase of 10% strain every 5 rounds). Five different high-strength hydrogels were then prepared (corresponding to A2B1C3, A2B2C4, A2B3C4, A2B4C4, and A2B5C4, respectively). Figure 11 Figure D is a comparison of the mechanical properties of five different high-strength hydrogels. (Source: [Insert Figure here]) Figure 11 This can further verify that letting it stand for approximately 24 hours is a more accurate parameter. Meanwhile, from... Figure 11 It can be seen that combining centrifugation and static conditions can further increase the stress and strain of the hydrogel, with the stress increasing from... Figure 11 The pressure was increased from around 70 MPa to around 130 MPa, and the strain was reduced from... Figure 11 The percentage was increased from 400% to 1500%, achieving unexpected technical results.

[0138] Example 10

[0139] 1) Use a 5mL disposable sterile syringe to inject the hydrophobic modification solution (fluorinated acrylic acid) into transparent silicone tubes with inner diameters of 0.5mm, 0.8mm, and 1.1mm respectively;

[0140] 2) Using a 5mL disposable sterile syringe, inject the hydrogel precursor solution obtained in Example 1 into transparent silicone tubes with inner diameters of 0.5mm, 0.8mm, and 1.1mm, respectively;

[0141] 3) Place the silicone tube filled with the hydrogel precursor solution in a constant temperature environment of 4℃ for 30 minutes to condense;

[0142] 4) Remove the silicone tube and place it under 405nm wavelength light for cross-linking and curing (to perform photo-cross-linking and curing of the hydrogel inside the silicone tube).

[0143] 5) Using a 50mL metal adjustable continuous drug delivery device, draw in deionized water, then screw the injection needle that matches the inner diameter of the silicone tube into the nozzle connection socket of the drug delivery device, insert the needle into the silicone tube, and use water pressure to squeeze the condensed and light-cured hydrogel into the ammonium sulfate solution.

[0144] 6) Perform stretching training and resting according to the method in Example 1 (steps (6) to (10)) to obtain strong and tough hydrogel monofilament fibers;

[0145] 7) The hydrogel single-strand fibers obtained in 6) are braided into ropes and webs to obtain hydrogel multi-strand fibers and hydrogel networks.

[0146] Figure 14 Figure A shows a single-strand fiber diagram of a strong and tough hydrogel, while figures C and D show nine-strand fibers of a strong and tough hydrogel. Figure 14 F in the diagram represents a strong and tough hydrogel network (during fabrication, liquid hydrogel is dropped onto the corresponding intersections, and the hydrogel solidifies (or can be further photocured) to fix multiple intersecting hydrogel fibers). Figure 14 G in the diagram is a schematic diagram for testing the mechanical properties of a strong and tough hydrogel network.

[0147] Application Example 1

[0148] Strong, tough hydrogel monofilament fibers were prepared according to the method in Example 10 (using a silicone tube with an inner diameter of 0.8 mm; however, after extruding the hydrogel and undergoing salt solution training, the hydrogel fibers became thinner, with the diameter of the monofilament fibers ranging from 0.2 mm to 0.6 mm, denoted as AS-1). Based on this, two-strand, three-strand, four-strand, and nine-strand fibers were fabricated (denoted as AS-2, AS-3, AS-4, and AS-9, respectively). The method for fabricating three-strand fibers was as follows: three fibers were arranged from left to right and named 1, 2, and 3. First, 1 was pressed down onto 2 from top to bottom and moved to the middle on the right; then, 3 was pressed down onto 2 from top to bottom and moved to the middle on the left; this process was repeated to obtain three-strand fibers. The method for making a four-strand fiber is as follows: Arrange the four fibers from left to right and name them 1, 2, 3, and 4. First, press 3 down onto 2 and move it to the left. Then, lift 1 up onto 2 and move it to the right. Next, press 4 down onto 3 and move it to the left from below 2. Then, press 1 down onto 2 and move it to the right. Next, lift 4 up onto 3 and move it to the left from above 2. Repeat this process to obtain a four-strand fiber. The method for making a nine-strand fiber is as follows: Weave three three-strand fibers using the same method as weaving three-strand fibers. Then, treat each three-strand fiber as a single-strand fiber and weave it again using the same method to obtain a nine-strand fiber. Figure 14 E shows the differences in mechanical properties between different strands of fiber.

[0149] Application Example 2

[0150] Multiple strong and tough hydrogel single-strand fibers with diameters of 0.5 mm, 0.8 mm, and 1.1 mm were prepared according to the method in Example 10. Figure 15 Figure A shows the comparison of mechanical properties of hydrogel networks with different diameters: keeping the spacing between the pores of the hydrogel network constant at 10 mm, and setting the diameter of the single fiber to 0.5 mm, 0.8 mm, and 1.1 mm respectively; Figure 15 To maintain the single fiber diameter at 0.8 mm, the mesh spacing in section B is set to be equal, with values ​​of 5 mm, 10 mm, and 20 mm. Figure 15 Figure C shows a comparison of the mechanical properties of the three hydrogel networks; keeping the single fiber diameter constant at 0.8 mm, the network pore spacing was set to unequal intervals of 5 mm & 10 mm, 5 mm & 20 mm, and 10 mm & 20 mm. Figure 15 Figure A shows a comparison of the mechanical properties of the three hydrogel networks.

[0151] A solid iron ball with a mass of 176.23g and a diameter of 35mm was placed on a hydrogel network, which could completely support it. The mass of the iron ball was 367.15 times that of the network, and the diameter of the iron ball was 79.55 times that of the network. Figure 16Figure A shows the hydrogel network supporting the steel ball, and Figure B shows a comparison of the diameter and mass of the steel ball and the hydrogel network.

[0152] A plastic bullet with a velocity of 15.2 m / s and an average impact force of 2.964 N was fired at the network, and the network was not damaged. Figure 16 C, D, and E are the results captured by the Phantom v2512 high-speed camera from Vision Research. The experimental parameters were set as follows: resolution 640×480; sampling rate 3000pps; exposure time 99.525 microseconds; and exposure index 400000. Figure 16 Figures C, D, and E in the image show the process of a bullet striking a hydrogel network, captured by a high-speed camera.

[0153] In summary, this invention achieves high-strength hydrogels by centrifuging, condensing, and photocrosslinking the hydrogel precursor solution, then placing the hydrogel in an ammonium sulfate solution for progressive axial cyclic stretching training, followed by immersion in PBS buffer. This process is repeated for one round, with an initial tensile strain of 30%. The tensile strain is increased by 3% every five rounds, for a total of 20 rounds. The hydrogel is then left to stand in an ammonium sulfate solution for 24 hours. This yields the high-strength hydrogel described in this invention, characterized by high efficiency, reduced experimental time, and lower economic costs. Based on this, strong and tough hydrogel monofilaments, multifilaments, and networks can be fabricated. The resulting networks can support iron balls 367 times their own weight and remain undamaged when subjected to plastic bullets with a velocity of 15.2 m / s and an average impact force of 2.964 N. This makes the hydrogel more suitable for regenerative medicine and tissue engineering research, demonstrating significant application prospects and commercial value.

[0154] The above-described embodiments are merely preferred embodiments of the present invention. It should be noted that the above embodiments are exemplary and should not be construed as limiting the present invention. For those skilled in the art, several changes, modifications, substitutions, and variations can be made without departing from the principle of the present invention, and these improvements and refinements should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing a high-strength hydrogel, characterized in that, include: The hydrogel precursor solution was centrifuged, condensed, and photocured sequentially. The photocured hydrogel was then subjected to progressive cyclic stretching training and immersion in PBS, and finally allowed to stand in a sulfate solution to obtain the high-strength hydrogel. The stretching training was carried out in a sulfate solution. The above cycle consisted of multiple rounds of stretching training and immersion in PBS, wherein adjacent rounds of stretching training and immersion in PBS formed a sub-cycle, and the tensile strain in each sub-cycle was greater than the tensile strain in the previous sub-cycle. The initial tensile strain of the first round of stretching training is 20%~40%; the number of sub-cycles is 2~10 sets; each sub-cycle includes 2~10 rounds of stretching training and immersion treatment in PBS; during each round of stretching training, the hydrogel is axially stretched 15~30 times in sulfate solution. The increase in tensile strain between two adjacent sub-cycles is 1% to 10%; During the centrifugation process, the centrifuge speed is 500~4000 rpm; the centrifugation time is 60~300s; During the settling process, the hydrogel is settling in the sulfate solution for 6 to 48 hours.

2. The method for preparing the high-strength hydrogel according to claim 1, characterized in that, The stretching rate of the hydrogel in sulfate solution was 1~15 mm / min; during each round of stretching training and immersion treatment in PBS, the hydrogel was immersed in PBS solution for 20~160 s.

3. The method for preparing the high-strength hydrogel according to claim 1, characterized in that, The condensation temperature is 2~8℃, and the condensation time is 900~2700s.

4. The method for preparing the high-strength hydrogel according to claim 1, characterized in that, The photocuring wavelength is 380nm~410nm, and the illumination time is 3~15s.

5. The method for preparing the high-strength hydrogel according to claim 1, characterized in that, The total number of stretching training and immersion treatment in PBS was 15-25 rounds; each subcycle included 4-6 rounds of stretching training and immersion treatment in PBS, and the tensile stress was the same in each round of each subcycle; the tensile strain increase between adjacent subcycles was 2%-5%; the resting time was 12-36 hours.

6. The method for preparing the high-strength hydrogel according to claim 1, characterized in that, The sulfate solution is an ammonium sulfate solution with a concentration of 35-65%; the hydrogel includes one or more of gelatin and hyaluronic acid.

7. A high-strength hydrogel, characterized in that, It is prepared by the preparation method according to any one of claims 1 to 6.

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