A high-rigidity, high-strength phase-separated hydrogel and its preparation method

Abstract

The present invention relates to the field of high-performance hydrogel preparation, and in particular to a high-rigidity, high-strength phase-separated hydrogel and a preparation method thereof. The method is a semi-interpenetrating bulk polymerization method, comprising the following steps: S1, mixing and dissolving a hydrophobic solid polymer, a hydrophilic liquid olefin monomer, an initiator, and a selectively added cross-linking agent to obtain a gel pre-reaction liquid; S2, shaping the gel pre-reaction liquid, initiating bulk polymerization, and obtaining a semi-interpenetrating bulk network polymer; S3, soaking the semi-interpenetrating bulk network polymer in water, and obtaining a high-rigidity, high-strength phase-separated hydrogel after hydration-induced phase separation. The hydrogel prepared by this method has a tensile strength of up to 1-50 MPa, a tensile modulus of up to 10-800 MPa, a water content of 25-80%, good mechanical properties and biocompatibility, and can be applied to the fields of biomedicine, flexible robots, fuel cells, etc.; the preparation step is simple and easy to scale production.

Description

Technical Field

[0001] The present invention belongs to the technical field of high-performance hydrogel preparation, and in particular relates to a high-rigidity, high-strength phase separation hydrogel and a preparation method thereof. Background Art

[0002] Hydrogels are highly water-rich materials with a three-dimensional network structure formed by polymers or biomacromolecules through chemical crosslinking, physical interactions, and supramolecular self-assembly. Due to their excellent hydrophilicity and biocompatibility, hydrogels are widely used in biomedicine, separation and filtration, drug delivery, and other fields. However, in practical applications, hydrogels must possess certain mechanical properties.

[0003] Hydrogels suitable for repairing and replacing load-bearing tissues in the human body (such as ligaments and cartilage) require high strength, high rigidity, and high load-bearing properties. Furthermore, the direct use of hydrogels as raw materials for medical consumables such as laryngeal tubes, gastric tubes, hernia patches, and vascular stents requires not only biocompatibility but also certain requirements for processing and mechanical strength. Currently, in numerous published papers, the weak mechanical properties of the prepared hydrogels remain the primary factor restricting their practical application.

[0004] 202310734725.2 discloses a high-strength, highly biocompatible, tough hydrogel, its preparation method, and application. By stretching the hydrogel in a saline solution to form an oriented, ordered structure, the method achieves a tensile strength of 6.67 MPa, significantly improving the hydrogel's mechanical properties. However, this method is only applicable to the preparation of hydrogel fibers and requires dozens of stretching cycles, making the preparation process cumbersome.

[0005] 202110639724.0 discloses a high-rigidity, high-strength, high-toughness lubricating copolymer hydrogel, and its preparation method and application; it uses monomers with rich hydrogen bonding sites: N-acryloyl urea amine and acryloyl carboxylic acid betaine, and prepares a high-rigidity, high-strength, high-toughness lubricating copolymer hydrogel through a secondary gel network construction method of the same monomers; however, its tensile modulus and tensile strength can only reach a maximum of 10.92 MPa and 4.34 MPa, respectively, which limits its application in high-load-bearing fields such as articular cartilage.

[0006] 202311686752.3 discloses a high-elasticity and high-toughness hydrogel, its preparation method and its application; it forms polymer fibers based on the interaction between polyvinyl alcohol and tannic acid, and obtains a hydrogel with low biological toxicity, high elasticity and high toughness after irradiation cross-linking; however, its tensile strength is only at the kPa level, and the presence of biodegradable substances in its components will affect its long-term stability.

[0007] 201110121052.0 discloses a method for preparing a pH-responsive nanohydrogel based on a semi-interpenetrating network structure. The method involves adding N-isopropylacrylamide monomer, an initiator, and a crosslinker to a polyacrylic acid aqueous solution. The monomer is then polymerized in situ under continuous stirring to produce a pH-responsive nanohydrogel. However, the resulting product is a water-dispersed gel particle, which cannot be used as a load-bearing structure. Summary of the Invention

[0008] In view of this, the present invention provides a high-rigidity, high-strength hydrogel and a preparation method thereof. Unlike the traditional method of preparing hydrogels in aqueous solution, the method provided by the present invention is semi-interpenetrating bulk polymerization. First, in the absence of any other solvent, a hydrophobic solid polymer is fully dissolved in a hydrophilic liquid monomer to obtain a gel pre-reaction liquid. Subsequently, bulk polymerization of the gel pre-reaction liquid is initiated to form a semi-interpenetrating bulk network polymer in the presence of an uncrosslinked polymer. Finally, the polymer is soaked in water to hydrate it. During this process, due to the huge difference in hydrophilicity between the two components constituting the polymer, the semi-interpenetrating bulk network polymer undergoes phase separation, forming a rigid glassy or crystalline hydrophobic polymer phase and a soft and tough hydrophilic hydrogel phase, ultimately obtaining a phase-separated hydrogel with high rigidity and high strength. The prepared hydrogel has excellent mechanical properties, and the preparation method is low-cost, simple, green and environmentally friendly, and suitable for industrial large-scale production.

[0009] The present invention provides a method for preparing a high-rigidity, high-strength phase-separated hydrogel, comprising the following steps:

[0010] S1, mixing and dissolving a hydrophobic solid polymer, a hydrophilic liquid olefin monomer, an initiator, and an optionally added cross-linking agent to obtain a gel pre-reaction solution;

[0011] S2, shaping the gel pre-reaction liquid, initiating bulk polymerization, and obtaining a semi-interpenetrating bulk network polymer;

[0012] S3. Soak the semi-interpenetrating bulk network polymer in water, and obtain a high-rigidity and high-strength phase-separated hydrogel after hydration-induced phase separation.

[0013] In step S1, the hydrophobic polymer includes one or more combinations of polymethyl methacrylate (PMMA), polymethyl acrylate (PMAA), polyethyl methacrylate (PMEA), polybutyl methacrylate (PMBA), polyisobornyl methacrylate (PIBMA), thermoplastic polyurethane elastomer (TPU), polyvinyl acetate (PVAc), polyvinyl butyral (PVB), polybutadiene (PB), polycaprolactone (PCL), poly(methyl methacrylate-co-ethyl acrylate) (P(MMA-co-EA)), and poly(methyl methacrylate-co-methacrylic acid) (P(MMA-co-MAAc)).

[0014] In step S1, the hydrophilic liquid olefin monomer includes one or more combinations of acrylic acid (AAc), methacrylic acid (MAAc), hydroxyethyl methacrylate (HEMA), N-vinyl formamide (NVF), polyethylene glycol methacrylate (PEGMA, Mn~360-1000), polyethylene glycol methyl ether methacrylate (Mn: ~475-2000), and methoxy polyethylene glycol acrylate (Mn~480-2000).

[0015] In step S1, the initiator includes one or more combinations of α-ketoglutaric acid (KA), 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (Irgacure 2959), diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), phenyl(2,4,6-trimethylbenzoyl)lithium phosphate (LAP), azobisisobutyronitrile (AIBN), 2,2'-azobisisobutylamidine dihydrochloride (V50), benzophenone (BP), dibenzoyl peroxide (BPO), and methyl benzoylformate (MBF).

[0016] In step S1, the cross-linking agent includes one or more combinations of N,N'-methylenebispropionamide (MBA), polyethylene glycol diacrylate (PEGDA, Mn~200-1000), polyethylene glycol dimethacrylate (PEGDMA, Mn: ~500-2000), 1,4-butanediol dimethacrylate (BDDMA), hexanediol dimethacrylate (HDDMA), and trimethylolpropane trimethacrylate (TMPTMA).

[0017] The mass ratio of the hydrophilic liquid olefin monomer to the hydrophobic polymer is 7:3-9:1.

[0018] Preferably, the mass ratio of the hydrophilic liquid olefin monomer to the hydrophobic polymer is 7:3-4:1.

[0019] Only with a specific ratio of hydrophilic liquid olefin monomer and hydrophobic polymer, the hydrophobic polymer can be dissolved in the hydrophilic liquid olefin monomer at a higher content, and after polymerization and hydration, a phase separation structure can be formed on the one hand, and entanglement can be formed on the other hand. Under the collaboration of the two, the effect of significantly improving the strength of the hydrogel can be achieved. When the hydrophilic olefin monomer content is too high, there are problems such as low and discontinuous hydrophobic phase content after hydration, and it is impossible to effectively transmit and disperse stress, and thus the hydrogel strength cannot be effectively improved. When the hydrophilic olefin monomer content is too low, there is a problem that the hydrophobic polymer cannot be completely dissolved, and thus a hydrogel cannot be formed.

[0020] The weight ratio of the hydrophobic polymer, the hydrophilic liquid olefin monomer, the initiator, and the crosslinking agent is 10-50:50-90:0.1-9:0-0.5.

[0021] Preferably, the weight ratio of the hydrophobic polymer, the hydrophilic liquid olefin monomer, the initiator, and the crosslinking agent is 10-30:70-90:0.2-3:0-0.25.

[0022] Preferably, the weight ratio of the hydrophobic polymer, the hydrophilic liquid olefin monomer, the initiator, and the crosslinking agent is 10-30:70-90:0.2-3:0.1-0.25.

[0023] In step S1, the dissolution temperature is 10-80° C., preferably 15-60° C., more preferably 20-50° C. The dissolution time is 60-2880 minutes, preferably 120-960 minutes, more preferably 180-720 minutes.

[0024] In step S2, the initiation method is photoinitiation or thermal initiation.

[0025] In photoinitiation, the irradiation time is 1-120 minutes, preferably 1-60 minutes, and more preferably 1-30 minutes.

[0026] In thermal initiation, the heating time is 4-48 hours, preferably 6-12 hours, and more preferably 8-10 hours.

[0027] In step S3, the hydration temperature is 10-100°C, preferably 15-80°C, and more preferably 20-60°C.

[0028] In step S3, the hydration time is 0.15-3 d, preferably 0.5-2 d, and more preferably 0.5-1 d.

[0029] The high-rigidity, high-strength semi-interpenetrating phase separation hydrogel prepared by the preparation method described above also falls within the protection scope of the present invention.

[0030] The application of the high-rigidity, high-strength semi-IPS-separated hydrogel described above in ligament repair, cartilage replacement, hernia patch or cannula replacement also falls within the scope of protection of the present invention.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] 1. The preparation method of this hydrogel is simple and easy to operate. The preparation process does not require additional organic solvents, the polymerization process is environmentally friendly, and it can be cast or coated to form a film. It is easy to synthesize and form, and is suitable for large-scale production.

[0033] 2. The hydrogel prepared by the present invention has excellent mechanical properties, with a tensile strength of up to 8-14 MPa and a tensile modulus of up to 260-525 MPa.

[0034] The core innovation of this invention focuses on the ingenious combination of a specific hydrophilic liquid monomer and a specific hydrophobic solid polymer to construct a hydrogel with excellent mechanical properties. The key lies in selecting the right hydrophilic liquid monomer that effectively dissolves the hydrophobic solid polymer and forms a semi-interpenetrating bulk polymer network. This in turn induces the formation of a phase-separated structure during hydration, while ensuring effective entanglement between the two polymer segments, significantly enhancing the strength of the hydrogel.

[0035] Specifically, in-depth research has revealed that not all hydrophilic liquid monomers interact well with hydrophobic solid polymers. For example, while DMAA and NVP can dissolve PMMA, they fail to form effective entanglements after polymerization and hydration, resulting in poor hydrogel strength. HEAA, on the other hand, cannot dissolve PMMA at all, making it impossible to prepare phase-separated hydrogels.

[0036] After systematic comparison, the present invention selected MAAc as the hydrophilic liquid monomer, which is highly effective in dissolving PMMA. Crucially, during the polymerization and hydration process, the PMAAc formed strongly entangled with PMMA. This entanglement not only promotes the stable formation of the phase-separated structure but also significantly enhances the mechanical properties of the hydrogel.

[0037] The present invention further confirms the advantages of PMMA in the selection of hydrophobic solid polymers. Compared to PCL and PE, PMMA is highly compatible with MAAc, enabling it to dissolve in MAAc at high concentrations and achieving ideal phase separation and entanglement during the subsequent hydration process, significantly enhancing the strength of the hydrogel. In contrast, PCL and MAAc can form phase separation but weak entanglement; and PE, due to its poor compatibility, is completely insoluble in MAAc. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Other features, objects and advantages of the present invention will become more apparent upon reading the detailed description of non-limiting embodiments with reference to the following drawings:

[0039] Figure 1 This is a photograph of the gel pre-reaction solution prepared by dissolving the polymer powder in the hydrophilic liquid monomer in Example 1;

[0040] Figure 2 The semi-interpenetrating polymer and phase-separated hydrogel before and after hydration in Example 1;

[0041] Figure 3 This is the tensile curve of PMMA / PMAAc hydrogel under optimal conditions. DETAILED DESCRIPTION

[0042] The present invention will be described in detail below with reference to the examples. The following examples will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that those skilled in the art may make several adjustments and improvements without departing from the scope of the present invention. These all fall within the scope of protection of the present invention.

[0043] In the following embodiments and comparative examples:

[0044] Polymethyl methacrylate (PMMA): LG, South Korea

[0045] Polyvinyl acetate (PVAc): Aladdin

[0046] Poly(methyl methacrylate-co-ethyl acrylate): Aladdin

[0047] Methacrylic acid (MAAc): Aladdin

[0048] Hydroxyethyl methacrylate (HEMA): TCI

[0049] TPO: Aladdin

[0050] Irgacure 2959: Ticia

[0051] LAP: Jizhi Chemical

[0052] PEGDA: Aladdin

[0053] MBA: Aladdin

[0054] N,N-dimethylacrylamide: Aladdin

[0055] N-vinyl pyrrolidone: Aladdin

[0056] Polycaprolactone: Perstorp, Sweden.

[0057] Examples 1-4

[0058] Examples 1-4 provide a high-rigidity, high-strength phase-separated hydrogel and a preparation method thereof.

[0059] Preparation of pre-reaction solution: According to the substances and amounts in Table 1, the hydrophobic solid polymer powder, hydrophilic liquid olefin monomer, photoinitiator, and crosslinker were stirred and mixed, and dissolved at 25°C for 720 minutes to obtain a uniform gel pre-reaction solution; Figure 1 The figure shows a photograph of a gel pre-reaction solution prepared by dissolving polymer powder in a hydrophilic liquid monomer in Example 1; (2) Preparation of a semi-interpenetrating polymer: the gel pre-reaction solution was cast in a 1 mm thick glass mold and irradiated with a 405 nm ultraviolet lamp for 30 minutes (Example 3) or a 365 nm ultraviolet lamp (Example 1 irradiation for 60 minutes, Example 2 irradiation for 90 minutes, Example 4 irradiation for 120 minutes) to initiate curing to obtain a semi-interpenetrating polymer;

[0060] (3) Hydration of semi-IPP: Soak the semi-IPP in 25℃ water for 1 day to obtain a high rigidity and high strength phase separation hydrogel; Figure 2 Shown are photos of the semi-interpenetrating polymer before and after hydration in Example 1.

[0061] Table 1

[0062]

[0063] Comparative Example 1

[0064] The difference between this comparative example and Example 1 is that methacrylic acid is replaced by N,N-dimethylacrylamide (DMAA).

[0065] Comparative Example 2

[0066] The difference between this comparative example and Example 1 is that methacrylic acid is replaced by N-vinylpyrrolidone (NVP).

[0067] Comparative Example 3

[0068] The difference between this comparative example and Example 1 is that methacrylic acid is replaced by N-n-propylacrylamide (NnPAM).

[0069] Comparative Example 4

[0070] The difference between this comparative example and Example 1 is that PMMA is replaced with polycaprolactone (Mw~80,000).

[0071] Comparative Example 5

[0072] The difference between this comparative example and Example 1 is that PMMA is not added.

[0073] Comparative Example 6

[0074] The difference between this comparative example and Example 1 is that the usage ratio of MAAc and PMMA is 95:5.

[0075] Comparative Example 7

[0076] This comparative example differs from Example 1 in that it utilizes a solvent exchange method. First, 21 g of MAAc, 49 g of PMMA, 1 g of TPO, and 0.09 g of PEGDA were dissolved in 230 mL of N,N-dimethylformamide. The resulting organogel was then irradiated with a 365 nm UV lamp for 60 minutes to form an organogel. The organogel was then immersed in 25°C water for 1 day to yield a phase-separated hydrogel.

[0077] Application performance testing:

[0078] Performance tests were performed on the hydrogels prepared in various examples and comparative examples.

[0079] Test method:

[0080] (1) Tensile test: A universal testing machine (KJ-1065A, Guangdong Kejian) was used to perform uniaxial tensile tests on the hydrogel samples. Before the test, the hydrogel samples were cut into dumbbell shapes (4 × 50 mm) using a cutter. The test temperature was room temperature, and the tensile rate was 100 mm / min. The tensile strength and tensile modulus were obtained from the tensile stress-strain curve. The tensile strength was the stress at the breaking point, and the elastic modulus was obtained from the slope of the linear fit of the initial elastic region in the stress-strain curve.

[0081] (2) Moisture content test: Use a forced air drying oven and a vacuum drying oven to dry the hydrogel sample to a constant weight. Weigh the sample mass before and after drying and calculate the moisture content. Moisture content (%) = (wet sample mass − dry sample mass) / wet sample mass × 100.

[0082] Table 2

[0083]

[0084] Figure 3 This is the tensile curve of the PMMA / PMAAc hydrogel in Example 1.

[0085] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art may make various variations or modifications within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A method for preparing a high-rigidity, high-strength phase-separated hydrogel, characterized in that: The steps include: S1, mixing and dissolving a hydrophobic solid polymer, a hydrophilic liquid olefin monomer, an initiator, and an optionally added cross-linking agent to obtain a gel pre-reaction solution; S2, shaping the gel pre-reaction liquid, initiating bulk polymerization, and obtaining a semi-interpenetrating bulk network polymer; S3, immersing the semi-IPN polymer in water to induce hydration and phase separation to obtain a high-rigidity and high-strength phase-separated hydrogel; The mass ratio of the hydrophilic liquid olefin monomer to the hydrophobic solid polymer is 7:3-9:1; In step S1, the hydrophobic solid polymer includes one or more combinations of polymethyl methacrylate, polymethyl acrylate, polyethyl methacrylate, polybutyl methacrylate, polyisobornyl methacrylate, poly(methyl methacrylate-co-ethyl acrylate), and poly(methyl methacrylate-co-methacrylic acid); In step S1, the hydrophilic liquid olefin monomer includes one or more combinations of acrylic acid, methacrylic acid, hydroxyethyl methacrylate, polyethylene glycol methacrylate, polyethylene glycol methyl ether methacrylate, and methoxy polyethylene glycol acrylate.

2. The preparation method according to claim 1, characterized in that In step S1, the initiator includes one or more combinations of α-ketoglutaric acid, 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide, phenyl(2,4,6-trimethylbenzoyl)phosphate lithium salt, azobisisobutyronitrile, 2,2'-azobisisobutylamidine dihydrochloride, benzophenone, dibenzoyl peroxide, and methyl benzoylformate.

3. The preparation method according to claim 1, characterized in that In step S1, the cross-linking agent includes one or more combinations of N,N'-methylenebisacrylamide, polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate, hexanediol dimethacrylate, and trimethylolpropane trimethacrylate.

4. The preparation method according to claim 1, characterized in that The mass ratio of the hydrophobic solid polymer, the hydrophilic liquid olefin monomer, the initiator, and the crosslinking agent is 10-50:50-90:0.1-9:0-0.

5.

5. The preparation method according to claim 1, characterized in that In step S1, the dissolution temperature is 10-80°C; and the dissolution time is 60-2880 minutes.

6. The preparation method according to claim 1, characterized in that In step S2, the initiation method is photoinitiation or thermal initiation; And / or, in step S3, the hydration temperature is 10-100° C., and the hydration time is 0.15-3 d.

7. A high-rigidity, high-strength phase-separated hydrogel prepared by the preparation method according to any one of claims 1 to 6.

8. Use of the hydrogel according to claim 7 in ligament repair, cartilage replacement, hernia patch or cannula replacement.

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