A four-arm polyethylene glycol amine and a preparation method and application thereof

Abstract

Four-arm polyethylene glycol amine and preparation method and application thereof, relate to the technical field of high polymer materials, and solve the problem of poor comprehensive performance such as strength, fatigue resistance and swelling resistance when the traditional double network hydrogel is applied to the preparation of cartilage repair materials in the prior art. The four-arm polyethylene glycol amine provided by the application has a molecular weight of 10 kDa or 40 kDa. Four-arm polyethylene glycol, phthalimide, diisopropyl azodicarboxylate and triphenylphosphine are subjected to Mitsunobu reaction and hydrazinolysis to obtain four-arm polyethylene glycol amine with a molecular weight of 10 kDa. Four-arm polyethylene glycol, phthalimide, diisopropyl azodicarboxylate and triphenylphosphine are subjected to Mitsunobu reaction and hydrazinolysis to obtain four-arm polyethylene glycol amine with a molecular weight of 40 kDa. The double network hydrogel prepared from the four-arm polyethylene glycol amine has excellent comprehensive performance such as high mechanical strength, fatigue resistance, self-recovery and swelling resistance, and can be applied to the preparation of cartilage-like materials.

Description

Technical Field

[0001] This invention relates to the field of polymer materials technology, specifically to a four-armed polyethylene glycolamine, its preparation method, and its application in the preparation of cartilage-like materials. Background Technology

[0002] In recent years, hydrogels have emerged as ideal cartilage replacement materials due to their excellent water absorption, biocompatibility, environmental responsiveness, and controllable physicochemical properties. However, existing hydrogels currently suffer from insufficient mechanical strength, poor fatigue resistance, easy swelling, and structural instability when subjected to external mechanical stress and prolonged use, making it difficult to meet the requirements of articular cartilage for long-term high-intensity loads and complex motion environments. Therefore, how to improve the mechanical strength, durability, and structural stability of materials while ensuring biocompatibility is a pressing technical problem that needs to be solved in the application of hydrogels in cartilage repair materials.

[0003] To address these issues, researchers proposed the concept of "dual-network hydrogels" in 2003, achieving a breakthrough in improving the mechanical properties of hydrogels. These hydrogels typically consist of two interconnected polymer networks with different physical properties. The brittle network fractures under stress, acting as an energy dissipation unit, while the flexible network maintains overall structural stability, significantly improving the material's strength, toughness, and environmental adaptability. Compared to traditional single-network hydrogels, dual-network hydrogels can withstand higher tensile and compressive forces, exhibiting superior ductility and durability, thus attracting widespread attention in the field of cartilage repair materials. However, the mechanical strength of existing dual-network hydrogels still lags behind that of natural cartilage. Under long-term, high-load, repeated stress, they are prone to fatigue damage and structural degradation, making it difficult to maintain stable support. Furthermore, existing dual-network hydrogels, as cartilage materials, are prone to volume expansion and tissue mismatch in body fluid environments, affecting repair efficacy and post-implantation stability. Therefore, how to further improve mechanical strength, fatigue resistance and swelling stability while ensuring its excellent biocompatibility is the core problem that needs to be solved in the application of dual-network hydrogels in the field of cartilage repair. Summary of the Invention

[0004] To address the shortcomings of traditional dual-network hydrogels in the preparation of cartilage repair materials, particularly in terms of overall performance such as strength, fatigue resistance, and swelling resistance, this invention proposes a four-armed polyethylene glycol amine, its preparation method, and its application. The technical solution of this invention is as follows:

[0005] A method for preparing a four-armed polyethylene glycolamine, wherein the molecular weight of the four-armed polyethylene glycolamine is 10 kDa or 40 kDa;

[0006] The preparation steps of the tetra-armed polyethylene glycolamine with a molecular weight of 10 kDa are as follows: tetra-armed polyethylene glycol, phthalimide, diisopropyl azodicarboxylate and triphenylphosphine are subjected to photo-extending reaction and hydrazide hydrolysis to obtain a tetra-armed polyethylene glycolamine with a molecular weight of 10 kDa.

[0007] The preparation steps of the four-armed polyethylene glycolamine with a molecular weight of 40 kDa are as follows: four-armed polyethylene glycol, triethylamine, methanesulfonyl chloride, phthalimide and diisopropyl azodicarboxylate are subjected to photoelongation reaction and hydrazide hydrolysis to obtain a four-armed polyethylene glycolamine with a molecular weight of 40 kDa.

[0008] Further, the preparation steps of the 10 kDa tetra-armed polyethylene glycolamine are as follows: tetra-armed polyethylene glycol, phthalimide, and triphenylphosphine are dissolved in anhydrous tetrahydrofuran. A tetrahydrofuran solution containing diisopropyl azodicarboxylate is added dropwise, and the mixture is stirred for one week. The solvent is removed, the residue is dissolved and filtered, extracted, and the organic phase is dried with anhydrous sodium sulfate, filtered, and concentrated. The product is precipitated three times from the organic phase using diethyl ether to obtain a pale yellow powder. The pale yellow powder is dissolved in tetrahydrofuran and refrigerated, filtered at room temperature, and the filter cake is dried. Hexane is added and the mixture is slurried twice, filtered, and air-dried to obtain a 10 kDa monomeric tetra-armed polyethylene glycolamine. The pale yellow powder is refrigerated in tetrahydrofuran for 48 h. The molar ratio of tetra-armed polyethylene glycol, phthalimide, diisopropyl azodicarboxylate, and triphenylphosphine is 1:5:5:5.

[0009] Further, the preparation steps of the tetra-armed polyethylene glycolamine with a molecular weight of 40 kDa are as follows: Triethylamine and methanesulfonyl chloride are added to an anhydrous dichloromethane solution containing tetra-armed polyethylene glycol, and the reaction is carried out in an ice bath. After the reaction is completed, the temperature is increased and the mixture is stirred. The reactants are purified by slurrying with diethyl ether to obtain an intermediate. The intermediate, phthalimide, and diisopropyl azodicarboxylate are dissolved in anhydrous tetrahydrofuran and reacted. The product is dissolved in ethanol, 80% hydrazine hydrate is added, and the mixture is refluxed. The crude product is dissolved and filtered, extracted, and the organic phase is dried with anhydrous sodium sulfate, filtered, and concentrated. The product is precipitated three times from the organic phase using diethyl ether to obtain a brown powder. The brown powder is dissolved in tetrahydrofuran and refrigerated, filtered at room temperature, and the filter cake is dried. Hexane is added and the mixture is slurryed again, filtered, and air-dried to obtain a product with a molecular weight of 40 kDa. The monomer is a four-armed polyethylene glycolamine of kDa; the molar ratio of the four-armed polyethylene glycol, triethylamine, methanesulfonyl chloride, phthalimide and diisopropyl azodicarboxylate is 1:4.3:1.3:4.2:5.

[0010] Furthermore, the reaction time in the ice bath environment is 8 hours; the temperature is raised to 25°C after the reaction is completed; and the stirring time is 48 hours.

[0011] Furthermore, the intermediate, phthalimide, and diisopropyl azodicarboxylate are dissolved in anhydrous tetrahydrofuran at a reaction temperature of 60°C for 3 days.

[0012] Furthermore, the reflux reaction time is 8 h; the brown powder is dissolved in tetrahydrofuran and refrigerated for 48 h.

[0013] A four-armed polyethylene glycolamine was prepared by the method described above.

[0014] One application of the above-mentioned four-armed polyethylene glycolamine is in the preparation of cartilage-like materials.

[0015] Furthermore, the four-armed polyethylene glycolamine is used in the preparation of a four-armed polyethylene glycolamine-polyacrylic acid dual-network hydrogel.

[0016] Furthermore, the preparation steps of the four-armed polyethylene glycolamine-polyacrylic acid dual-network hydrogel are as follows:

[0017] S1: Add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide to a phosphate buffer containing four-armed polyethylene glycolamine, stir, add polyacrylic acid to react, and obtain the bottom hydrogel material;

[0018] S2: Immerse the bottom hydrogel material in FeCl3 solution, remove it and inject it into the mold, remove air bubbles, and perform continuous freeze-thaw cycles to obtain a four-arm polyethylene glycolamine-polyacrylic acid double network hydrogel.

[0019] The molar ratio of the four-armed polyethylene glycolamine to polyacrylic acid is 1:0.75; the molar ratio of the four-armed polyethylene glycolamine to 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide is 1:2.2:2.5.

[0020] Compared with existing technologies, this invention solves the problem of poor overall performance, such as strength, fatigue resistance, and swelling resistance, when traditional dual-network hydrogels are used in the preparation of cartilage repair materials. Specifically, the beneficial effects are as follows:

[0021] 1. Excellent fatigue resistance and self-healing properties: This invention constructs a dual-network structure with both flexible segments and strong interactions by controlling the molecular weight of the four-arm polyethylene glycolamine. This allows the hydrogel to effectively disperse and dissipate external stress during cyclic loading, avoiding structural damage caused by stress concentration. Thus, it maintains significant mechanical stability even under repeated compression and tension. At 80% compressive strain, the dual-network hydrogel exhibits a stress as high as 30.8 MPa and a toughness as high as 3.82 MJ / m. 3The peak stress after 10 cycles of loading and unloading remained at 99.8% of the initial stress value, and the recovery rate of elastic modulus and dissipated energy during the short-term recovery process was close to 100%. This fully verifies the fatigue resistance and rapid self-recovery characteristics of the dual-network hydrogel provided by this invention under long-term stress environment, and it has potential application value in the field of cartilage-like replacement materials.

[0022] 2. High strength and significant anti-swelling properties: This invention introduces rigid polyacrylic acid segments into a four-armed polyethylene glycolamine flexible network, forming an interpenetrating double network structure. This allows for effective energy transfer and dispersion under external forces, significantly improving the overall strength and structural stability of the material, effectively increasing peak stress and enhancing deformation resistance. Simultaneously, the polycarboxyl groups in the polyacrylic acid segments form stable hydrogen bonds with water molecules, limiting excessive water intrusion and significantly reducing the swelling rate (1.5). This allows the hydrogel to maintain low volume change and long-term stability in various solution environments (deionized water, physiological saline, and high-concentration urea solution). This synergistic improvement in strength and anti-swelling properties enables the hydrogel to maintain a stable three-dimensional structure in simulated body fluid environments, ensuring its applicability and durability as a cartilage-like substitute material in complex physiological environments.

[0023] 3. Suitable for large-scale applications: The dual-network hydrogel prepared using four-arm polyethylene glycolamine provided by this invention possesses excellent comprehensive properties such as high mechanical strength, fatigue resistance, self-healing, and anti-swelling properties. The preparation process is mild, simple, and uses readily available and low-cost raw materials, avoiding reliance on expensive and rare materials or high-energy-consuming processes. The preparation process is green and environmentally friendly, with good economic feasibility, and meets the needs of sustainable development. It can be widely used in the preparation of materials in fields such as articular cartilage repair, artificial soft tissue replacement, medical cushioning materials, and flexible biodevices. Attached Figure Description

[0024] Figure 1 The 1H NMR spectrum of a 10 kDa monomeric four-armed polyethylene glycolamine.

[0025] Figure 2 Infrared spectrum of a four-armed polyethylene glycolamine (10 kDa)-polyacrylic acid double network hydrogel;

[0026] Figure 3 The 1H NMR spectrum of a 40 kDa monomeric four-armed polyethylene glycolamine.

[0027] Figure 4 Infrared spectrum of a four-armed polyethylene glycolamine (40 kDa)-polyacrylic acid double network hydrogel;

[0028] Figure 5 The stress-strain curve of the dual-network hydrogel;

[0029] Figure 6 The graph shows the elastic modulus and dissipation energy of the dual-network hydrogel.

[0030] Figure 7 The toughness diagram of the dual-network hydrogel is shown.

[0031] Figure 8 Stress-strain curves of a four-armed polyethylene glycolamine-polyacrylic acid dual-network hydrogel under loading-unloading cycles;

[0032] Figure 9 The mechanical properties of the dual-network hydrogel change under different cycles;

[0033] Figure 10 The stress-strain curves of the dual-network hydrogel at different recovery times are shown.

[0034] Figure 11 The mechanical property recovery of the dual-network hydrogel;

[0035] Figure 12 Stress-strain curves for cyclic tensile testing of dual-network hydrogels;

[0036] Figure 13 The mechanical property changes of the dual-network hydrogel under cyclic tensile testing;

[0037] Figure 14 The results show the swelling properties of the dual-network hydrogel. Detailed Implementation

[0038] To make the technical solutions of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. It should be noted that the following embodiments are only used to better understand the technical solutions of the present invention and should not be construed as limiting the present invention.

[0039] Example 1.

[0040] P1: Dry tetrahydrofuran (5 g, 2 mmol), phthalimide (1.47 g, 10 mmol, 5 eq), and triphenylphosphine (2.62 g, 10 mmol, 5 eq) were dissolved in 40 mL of anhydrous tetrahydrofuran. 10 mL of a tetrahydrofuran solution containing diisopropyl azodicarboxylate (2.03 g, 10 mmol, 5 eq) was added dropwise. The mixture was stirred at room temperature for 7 days. The solvent was removed under vacuum. The residue was dissolved in water and filtered. The aqueous solution was saturated with sodium chloride and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The product was precipitated three times from the organic phase using diethyl ether to obtain a pale yellow powder. The pale yellow powder was dissolved in tetrahydrofuran (1 g / 5 mL) and refrigerated for 48 h. The mixture was filtered at room temperature (with an equal volume of n-hexane 1 g / 5 mL added). After drying the filter cake, n-hexane (1 g / 10 mL) was added. (mL) The mixture was pulped twice at room temperature, filtered, and air-dried to obtain a monomeric four-armed polyethylene glycolamine with a molecular weight of 10 kDa. The 1H NMR spectrum of the 10 kDa monomeric four-armed polyethylene glycolamine is shown below. Figure 1 As shown, the NMR characterization results are as follows: 1 H NMR (500 MHz, Chloroform) δ 3.86 – 3.45 (m, 908H), 3.35 (s, 8H), 1.86 (m, 8H), 1.92 (s, 8H);

[0041] P2: Weigh four-armed polyethylene glycolamine (10 kDa), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide, and polyacrylic acid (5.76 kDa) in a molar ratio of 1:2.2:2.5:0.75; dissolve the four-armed polyethylene glycolamine (10 kDa) in phosphate buffer, then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide, stir at room temperature for 10 min, then add polyacrylic acid to the system and react at pH 7 for 8 h to obtain the bottom hydrogel material;

[0042] P3: The bottom hydrogel material was immersed in FeCl3 solution for 3 h, then removed and poured into a mold. It was allowed to stand at room temperature to remove air bubbles, then placed in a -25°C freezer for 24 h, followed by 5 h at room temperature. This freeze-thaw cycle was repeated 10 times to obtain a four-armed polyethylene glycolamine-polyacrylic acid dual-network hydrogel. The infrared spectral results of the four-armed polyethylene glycolamine-polyacrylic acid dual-network hydrogel are shown below. Figure 2 As shown, at 3222cm -1 The absorption peak appearing at 1690 cm⁻¹ is the stretching vibration peak of the amino group. -1 The stretching vibration peak of the carbonyl group of the amide bond appears at 1520 cm⁻¹.-1 The bending vibration peak of the amino group appears at 1129 cm⁻¹. Due to the intramolecular hydrogen bonding, the electron cloud shifts back towards the electronegative atom, corresponding to a shift of the infrared absorption peak towards lower wavenumbers, reaching 1129 cm⁻¹. -1 The peak at this point represents the stretching vibration of the ether bond, indicating that the hydrogel contains the above-mentioned groups, thus proving the successful preparation of the hydrogel sample.

[0043] Example 2.

[0044] P1: Triethylamine (4.3 eq) and methanesulfonyl chloride (1.3 eq) were added to an anhydrous dichloromethane solution containing tetra-armed polyethylene glycol in a three-necked flask. The reaction was carried out in an ice bath for 8 h, then heated to 25 °C and stirred for 48 h. After the reaction was completed, the reactants were purified by slurrying with diethyl ether to obtain an intermediate. The intermediate, phthalimide (4.2 eq), and diisopropyl azodicarboxylate (5 eq) were dissolved in anhydrous tetrahydrofuran and reacted at 60 °C for 3 days. The product was dissolved in ethanol, and 80% hydrazine hydrate (11.5 eq) was added. The mixture was refluxed for 8 h. After the reaction was completed, the crude product was dissolved in water and filtered. The aqueous solution was saturated with sodium chloride and extracted with dichloromethane. The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated. The product was precipitated from the organic phase three times with diethyl ether to obtain a brown powder. The brown powder was dissolved in tetrahydrofuran (1 g / 10 mL) and refrigerated for 48 h. The mixture was then filtered at room temperature (with an equal volume of n-hexane added). After drying the filter cake, hexane (1 g / 30 mL) was added, and the mixture was stirred twice at room temperature. The mixture was then filtered and air-dried to obtain a monomeric four-armed polyethylene glycolamine with a molecular weight of 40 kDa. The 1H NMR spectrum is shown below. Figure 3 As shown, the NMR characterization results are as follows: 1 H NMR (500 MHz, Chloroform) δ 3.89 – 3.38 (m, 3636H), 3.32 (s, 8H), 3.17 (m, 8H), 1.85 (s, 8H);

[0045] P2: Weigh four-armed polyethylene glycolamine (40 kDa), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide, and polyacrylic acid (5.76 kDa) in a molar ratio of 1:2.2:2.5:0.75; dissolve the four-armed polyethylene glycolamine (40 kDa) in phosphate buffer, then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide, stir at room temperature for 10 min, then add polyacrylic acid to the system and react at pH 7 for 8 h to obtain the bottom hydrogel material;

[0046] P3: The bottom hydrogel material was immersed in FeCl3 solution for 3 h, then removed and poured into a mold. It was allowed to stand at room temperature to remove air bubbles, then placed in a -25°C freezer for 24 h, followed by 5 h at room temperature. This freeze-thaw cycle was repeated 10 times to obtain a four-armed polyethylene glycolamine-polyacrylic acid dual-network hydrogel. The infrared spectral results of the four-armed polyethylene glycolamine-polyacrylic acid dual-network hydrogel are shown below. Figure 4 As shown, it can be found at 3230cm. -1 The absorption peak appearing at 1660 cm⁻¹ is the stretching vibration peak of the amino group. -1 The stretching vibration peak of the carbonyl group exhibiting the amide bond appears at 1500 cm⁻¹. -1 The bending vibration peak of the amino group appears at 1120 cm⁻¹. Due to the intramolecular hydrogen bonding, the electron cloud shifts back towards the electronegative atom, corresponding to a shift of the infrared absorption peak towards lower wavenumbers, at 1120 cm⁻¹. -1 The peak at this point represents the stretching vibration of the ether bond, indicating that the hydrogel contains the above-mentioned groups, thus proving the successful preparation of the hydrogel sample.

[0047] The four-arm polyethylene glycolamine-polyacrylic acid double-network hydrogels prepared in Examples 1 and 2 were made into cylinders and subjected to compression tests at a compression rate of 10 mm / min. Figure 5 The figure shows the stress-strain curve of a four-armed polyethylene glycolamine-polyacrylic acid dual-network hydrogel. As can be seen from the figure, when a four-armed polyethylene glycolamine with a molecular weight of 40 kDa is used as the crosslinking backbone, the compressive stress of the resulting dual-network hydrogel reaches 30.8 MPa, significantly higher than that of the corresponding hydrogel prepared with a molecular weight of 10 kDa. This demonstrates that a high molecular weight four-armed polyethylene glycolamine helps to improve the compressive strength of the hydrogel. Figure 6 The figure shows the elastic modulus and dissipation properties of a four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel. As can be seen from the figure, the dual-network hydrogel prepared from four-arm polyethylene glycolamine with a molecular weight of 40 kDa has an elastic modulus of 9.45 MPa and a dissipation energy of 0.31 MJ / m. 3 ,like Figure 7 As shown, the double-network hydrogel prepared from four-arm polyethylene glycolamine with a molecular weight of 40 kDa has a toughness of 3.82 MJ / m. 3 The results showed that the high molecular weight (40 kDa) four-arm polyethylene glycolamine was superior to the corresponding hydrogel prepared with a molecular weight of 10 kDa, demonstrating that high molecular weight (40 kDa) four-arm polyethylene glycolamine can effectively improve the mechanical properties of the dual-network hydrogel. The obtained material exhibits high strength, high modulus, and excellent toughness, showing that the dual-network hydrogel prepared in this invention has broad application potential in cartilage replacement, flexible support materials, and impact-resistant sustained-release materials. Subsequent studies will select the 40 kDa four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel for further performance testing.

[0048] Fatigue resistance test:

[0049] The four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel prepared in Example 2 was subjected to 10 cycles of load-unload experiments under compression conditions of 50% stress and a loading rate of 10 mm / min, and under tensile conditions of 100% stress and a loading rate of 100 mm / min. Figure 8 The figure shows the cyclic loading-unloading stress-strain curves of a four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel. As can be seen from the figure, the cyclic stress-strain curves of this hydrogel remain highly overlapping after multiple cycles, without significant shift or attenuation. Figure 9 The mechanical properties of the four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel were further demonstrated under different cycles. As shown in the figure, the peak stress of the dual-network hydrogel remained at approximately 99.8% of its initial value, and the dissipated energy was stably maintained at approximately 24.68 kJ / m². 3 This indicates that the hydrogel still possesses excellent fatigue resistance under long-term repeated stress.

[0050] Self-healing performance test:

[0051] The self-healing properties of the four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel prepared in Example 2 were tested, such as... Figure 10 The figure shows the stress-strain curves of the four-arm polyethylene glycolamine-polyacrylic acid double network hydrogel at different recovery times. As the recovery time increases, the mechanical properties of the material gradually recover. When the recovery time reaches 100 s, the overall recovery rate is as high as 99.99%. Figure 11 The mechanical property recovery of the four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel at different recovery times is presented. It can be observed that after 100 s of recovery, the recovery rate of both elastic modulus and dissipated energy reaches 100%, fully demonstrating that the dual-network hydrogel possesses rapid and efficient self-recovery capabilities. In summary, the four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel prepared in this invention not only exhibits excellent fatigue resistance but also possesses outstanding rapid self-recovery capabilities, providing strong support for the development of cartilage-like replacement materials.

[0052] Tensile property test:

[0053] The four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel prepared in Example 2 was stretched at a rate of 100 mm / min until the set strain was reached, and then restored to its initial state at the same rate. This loading-unloading cycle was repeated 10 times. Figure 12 The stress-strain curves for cyclic tensile testing of the four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel are shown in the figure. As can be seen from the figure, the cyclic tensile stress-strain curves remain highly overlapping after 10 cycles, indicating no significant performance degradation. Figure 13 To investigate the mechanical property changes of the four-arm polyethylene glycolamine-polyacrylic acid dual-network hydrogel under cyclic stretching, the results showed that after 10 cycles of stretching, the peak stress of the hydrogel was 0.84 MPa, maintaining 98.85% of the initial value, which fully demonstrates that the dual-network hydrogel has excellent fatigue resistance and structural stability.

[0054] Swelling performance test:

[0055] The four-armed polyethylene glycolamine-polyacrylic acid dual-network hydrogels prepared in Example 2, cut to 20 mm × 20 mm, were placed in deionized water, 0.9% NaCl solution, and 5 mol / L urea solution, respectively. Swelling experiments were conducted at 37°C. The samples were periodically removed, dried, and weighed within the range of 0–100 h until the samples reached swelling equilibrium. Figure 14 As shown, the hydrogel swells significantly faster in urea solution than in other systems, expanding rapidly within 2 hours, gradually stabilizing after 6 hours, and essentially ceasing mass change after 10 hours, with a final swelling ratio of 3. In deionized water and 0.9% NaCl solution, the hydrogel's swelling ratio is approximately 1.5 within the first 2 hours, after which it rapidly reaches saturation. This demonstrates that the dual-network hydrogel prepared in this invention not only maintains good structural stability under high ion concentrations and urea environments, but its low swelling and long-term stability also give it significant advantages as a cartilage-like substitute material.

[0056] In summary, this invention constructs a dual-network structure with both flexible segments and strong interactions by controlling the molecular weight of the four-armed polyethylene glycolamine and the crosslinking ratio with polyacrylic acid. This effectively improves the overall strength and mechanical stability of the material, while also exhibiting excellent comprehensive properties such as high mechanical strength, fatigue resistance, self-healing, and anti-swelling properties. It can be widely used in the preparation of materials in fields such as articular cartilage repair, artificial soft tissue replacement, medical cushioning materials, and flexible biodevices.

[0057] The above description of the embodiments is only for the purpose of helping to understand the method and core ideas of the present invention. It should be noted that those skilled in the art can make several improvements and modifications to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

[0058] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. Use of a four-armed polyethylene glycol amine, characterized in that, Be applied to preparation of cartilage-like material Be applied to preparation of four-arm polyethylene glycol amine-polyacrylic acid double network hydrogel The preparation steps of the four-arm polyethylene glycol amine-polyacrylic acid double network hydrogel are: S1: adding 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide into phosphate buffer solution containing four-arm polyethylene glycol amine, stirring, adding polyacrylic acid for reaction to obtain bottom layer hydrogel material; S2: soaking the bottom layer hydrogel material in FeCl3 solution, pouring into a mold after taking out, removing bubbles, and performing continuous freeze-thaw cycle to obtain four-arm polyethylene glycol amine-polyacrylic acid double network hydrogel; The molar ratio of the four-arm polyethylene glycol amine and polyacrylic acid is 1:0.75; the molar ratio of the four-arm polyethylene glycol amine, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide is 1:2.2:2.5; The molecular weight of the four-arm polyethylene glycol amine is 40 kDa; The preparation steps of the four-arm polyethylene glycol amine with a molecular weight of 40 kDa are: subjecting four-arm polyethylene glycol, triethylamine, methylsulfonyl chloride, phthalimide and azobisdimethylvaleric acid diisopropyl ester to Mitsunobu reaction and hydrazinolysis to obtain four-arm polyethylene glycol amine with a molecular weight of 40 kDa.

2. Use of a four-armed polyethylene glycol amine according to claim 1, characterized in that, The preparation steps of the four-arm polyethylene glycol amine with a molecular weight of 40 kDa are as follows: adding triethylamine and methylsulfonyl chloride into anhydrous dichloromethane solution containing four-arm polyethylene glycol, reacting in an ice bath environment, stirring after the reaction is completed, purifying the reaction product by beating with diethyl ether to obtain an intermediate; dissolving the intermediate, phthalimide and azobisdimethylvaleric acid diisopropyl ester in anhydrous tetrahydrofuran for reaction, dissolving the product in ethanol, adding 80% hydrazine hydrate, refluxing for reaction, dissolving and filtering the crude product, extracting, drying the organic phase with anhydrous sodium sulfate, filtering and concentrating; precipitating the product from the organic phase with diethyl ether for three times to obtain brown powder; dissolving the brown powder in tetrahydrofuran, cold storage, vacuum filtration at room temperature, drying the filter cake, adding n-hexane for twice beating, vacuum filtration, and naturally airing to dry to obtain four-arm polyethylene glycol amine monomer with a molecular weight of 40 kDa; the molar ratio of the four-arm polyethylene glycol, triethylamine, methylsulfonyl chloride, phthalimide and azobisdimethylvaleric acid diisopropyl ester is 1:4.3:1.3:4.2:

5.

3. Use of a four-armed polyethylene glycol amine according to claim 2, characterized in that, The reaction time in the ice bath environment is 8 h; the temperature is increased to 25℃ after the reaction is completed; and the stirring time is 48 h.

4. The use of a four-armed polyethylene glycol amine according to claim 2, characterized in that The reaction temperature of the intermediate, phthalimide and azobisdimethylvaleric acid diisopropyl ester in anhydrous tetrahydrofuran is 60℃, and the reaction time is 3 days.

5. The use of a four-armed polyethylene glycol amine according to claim 2, characterized in that The refluxing reaction time is 8 h; and the cold storage time of the brown powder in tetrahydrofuran is 48 h.

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