A pHEMA hydrogel and a method for preparing the same

Abstract

The present application relates to a kind of PHEMA hydrogel and its preparation method, belong to hydrogel technical field, including the following mass parts raw materials: 2-hydroxyethyl methacrylate, reinforcing agent, solvent, crosslinking agent, initiator and slow-release agent;Preparation method includes the following steps: crosslinking agent is dispersed in 2-hydroxyethyl methacrylate, then reinforcing agent and slow-release agent are dispersed in solvent, and ultrasonic treatment is carried out, subsequently initiator is added dropwise to system, and make the reaction reflux 3 hours at 80 DEG C, after reaction, wash with deionized water, and dry, obtain PHEMA hydrogel.The technical scheme in the present application, by incorporating [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide, can enhance biocompatibility and antifouling performance, also can adjust the water content and pore of hydrogel, play the role of balancing optical transparency and oxygen permeability.

Description

Technical Field

[0001] This invention belongs to the field of hydrogel technology, specifically, it relates to a PHEMA hydrogel and its preparation method. Background Technology

[0002] Hydrogels, as the name suggests, are a type of gel-like polymer that uses water as a dispersion medium. Their molecular structure contains numerous hydrophilic groups, enabling them to bind strongly with water. Structurally, they possess a cross-linked three-dimensional network structure, allowing a large amount of water to permeate the macromolecules, resulting in excellent viscoelasticity. The study of hydrogels has a long history and is currently very active. Scientists are developing hydrogels with even better performance, and their applications are being greatly expanded. In this era of rapid scientific and technological development, competition for novel functional materials is becoming increasingly fierce. Due to their unique and outstanding properties, hydrogels are receiving increasing attention, demonstrating the vast potential of hydrogel research.

[0003] Ideal hydrogel contact lenses typically require a combination of desirable properties, such as high optical transparency, good oxygen permeability, excellent biocompatibility, high water content, and strong mechanical properties. While HEMA-based hydrogels have demonstrated excellent biocompatibility in many applications, HEMA-based hydrogel contact lenses manufactured through bulk polymerization often suffer from low water content (below 40%), poor oxygen permeability, and low light transmittance. Summary of the Invention

[0004] The purpose of this invention is to provide a PHEMA hydrogel and its preparation method. Boric acid is used as a linker between 2-hydroxyethyl methacrylate and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, allowing the boric acid to participate in the crosslinking of 2-hydroxyethyl methacrylate. Increasing the number of internal hydroxyl groups in the 2-hydroxyethyl methacrylate hydrogel achieves better bonding between [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide and the hydrogel, thus improving the hydrogel's transparency, biocompatibility, self-antibacterial properties, and antifouling performance.

[0005] Furthermore, by depositing polydopamine on the surface of mesoporous silica, amino and benzoquinone functional groups were introduced onto the surface of the mesoporous silica. The introduced amino functional groups can better adsorb hyaluronic acid, achieving continuous drug delivery to the eyes. The introduced benzoquinone functional groups can combine with branched polyethyleneimine through a Schiff base reaction. The mesoporous silica with branched polyethyleneimine then combines with glycidyl ether to achieve the introduction of vicinal diol. The introduced vicinal diol is dispersed in the hydrogel matrix along with the mesoporous silica, improving the oxygen permeability and water content of the hydrogel. In addition, vicinal diol can better combine with boron, achieving stable dispersion of nanoparticles and improving the stability of the hydrogel.

[0006] The technical problem to be solved by this invention is that although HEMA-based hydrogels have shown excellent biocompatibility in many applications, HEMA-based hydrogel contact lenses made by bulk polymerization usually have problems such as low water content (less than 40%), poor oxygen permeability and low light transmittance.

[0007] The objective of this invention can be achieved through the following technical solutions:

[0008] A PHEMA hydrogel comprises the following raw materials in parts by weight: 40-50 parts of 2-hydroxyethyl methacrylate, 30-40 parts of reinforcing agent, 20-30 parts of solvent, 1-2 parts of crosslinking agent, 0.5-1 part of initiator and 1-2 parts of sustained-release agent.

[0009] Furthermore, the reinforcing agent is an amphoteric compound [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, with the following structural formula:

[0010]

[0011] Furthermore, the sustained-release agent is prepared by the following steps:

[0012] A1. Place the drug-loaded silica modified with polydopamine and branched polyethyleneimine into an autoclave, add deionized water, seal the autoclave, and heat in a vacuum oven at 145°C for 6.5 hours. After cooling, wash repeatedly with water at 60-70°C until the rinsing solution becomes neutral. Then dry them under vacuum at 50°C for 24 hours to obtain the drug-loaded silica modified with branched polydopamine.

[0013] A2. Branched polydopamine-modified drug-loaded silica was dispersed in glycidyl ether and ethanol, and refluxed continuously in an oil bath at 80°C for 24 hours. Then, it was taken out and washed several times with deionized water, and dried under vacuum at 45°C to obtain a sustained-release agent.

[0014] The structural formula of the sustained-release agent is as follows:

[0015]

[0016] Furthermore, the mass ratio of polydopamine-modified drug-loaded silica, branched polyethyleneimine, and deionized water is 1:2:70;

[0017] The ratio of branched polydopamine-modified drug-loaded silica, glycidyl ether, and ethanol was 10 mg: 0.5 mL: 50 mL.

[0018] The structural formula of branched polyethyleneimine is as follows:

[0019]

[0020] The structural formula of glycidol is as follows:

[0021]

[0022] Furthermore, the polydopamine-modified drug-loaded silica is prepared by the following steps:

[0023] B1. Add nanoporous silica to 10 mmol / L Tris buffer solution, pH=8.5, and sonicate for 1 h. Then, add dopamine hydrochloride to the solution and stir magnetically for 24 h at room temperature. After the reaction is complete, centrifuge the mixture for 20 min, wash it three times with ethanol to remove unreacted monomers, and place the obtained solid in an oven to dry at 170 °C for 12 h to obtain polydopamine modified silica.

[0024] B2. Disperse polydopamine-modified silica in 10 mmol / L Tris buffer, pH 8.5, and add hyaluronic acid to the solution. Stir for 5 minutes at room temperature in the dark, and centrifuge at 20,000 rpm for 20 minutes. Remove the supernatant, wash the precipitate three times with deionized water, and freeze-dry to obtain polydopamine-modified drug-loaded silica.

[0025] The structural formula of hyaluronic acid is as follows:

[0026]

[0027] The structural formula of polydopamine-modified drug-loaded silica is as follows:

[0028]

[0029] Furthermore, the ratio of nanoporous silica, Tris-HCl buffer, and dopamine hydrochloride was 1 g: 100 mL: 0.2 g;

[0030] The ratio of polydopamine-modified silica, Tris buffer, and hyaluronic acid was 0.1 g: 10 mL: 5 mL.

[0031] Furthermore, nanoporous silica is prepared by the following steps:

[0032] C1. Mix cyclohexane, isooctyl alcohol, Triton X-100 and cetyltrimethylammonium bromide (CTAB) and stir for 30 minutes to form a transparent microemulsion. Add APTES dissolved in deionized water to the microemulsion, stir the mixture for 10 minutes, and then sonicate for 30 minutes to form a homogeneous solution.

[0033] C2. Tetraethoxysilane (TEOS), 3-aminopropyltriethoxysilane (TMAPS) and ammonia were added dropwise to the solution and stirred for 24 hours. Acetone was added, and the mixture was centrifuged at 8000 rpm for 10 minutes. The obtained nanoparticles were washed sequentially with ethanol, ultrapure water, glacial acetic acid and deionized water, and then freeze-dried to obtain nanoporous silica.

[0034] The volume ratio of cyclohexane, isooctyl alcohol, Triton X-100, CTAB, deionized water, and APTES was 72.6 mL: 17.64 mL: 16.87 mL: 15 mg: 4 mL: 10 μL;

[0035] The ratio of TEOS, TMAPS, ammonia, and acetone used is 640 μL: 370 μL: 800 μL: 40 mL.

[0036] Furthermore, the crosslinking agent is a polyhydroxy substance, and the polyhydroxy substance is boric acid.

[0037] Furthermore, the solvent is deionized water, and the initiator is potassium persulfate.

[0038] It should be noted that this invention takes into account that polymer hydrogels are typical soft, wet, and hydrophilic materials containing a large amount of water (up to >90%) in their cross-linked three-dimensional networks. HEMA-based hydrogels, typically synthesized through bulk polymerization, often encounter a common problem: they require high water content to achieve high oxygen permeability, but their transparency is also relatively low. Therefore, increasing the water content is achieved by incorporating other hydrophilic materials into the HEMA hydrogel network. Thus, these hybrid HEMA hydrogels can typically significantly increase their water content, but their oxygen permeability is greatly reduced.

[0039] Besides light transmittance and oxygen permeability for in vivo applications, the antifouling ability of hydrogels is another concern. Due to the non-specific adsorption of tear proteins (such as lysozyme), HEMA-based hydrogels often lose their antifouling ability in complex media. In many cases, HEMA-based hydrogels are modified with different antifouling materials to protect the gel from protein adsorption, cell adhesion, and in vivo foreign body reactions. Among different antifouling materials, zwitterionic polymers, composed of uniformly balanced positive and negatively charged groups, have shown ultra-low fouling resistance, resisting surface adsorption of various proteins, cells, and bacteria. Strong surface hydration is considered a key factor in the antifouling performance of polymers, simply because the tightly bound water layer around the polymer forms a physical and energy barrier to prevent biomolecules from adhering to the polymer surface. Unlike hydrophilic polymers that achieve surface hydration through hydrogen bonding, zwitterionic polymers achieve surface hydration through ion-induced hydration, which allows for a more robust binding of water molecules.

[0040] A method for preparing PHEMA hydrogel includes the following steps:

[0041] S1. Weigh out the raw materials according to the formula mass;

[0042] S2. The crosslinking agent is dispersed in 2-hydroxyethyl methacrylate and stirred continuously at room temperature for 15 min. Then, the reinforcing agent and the slow-release agent are dispersed in the solvent and sonicated for 20 min. Subsequently, the initiator is added dropwise to the system and the reaction is refluxed at 80°C under magnetic stirring for 3 hours. After the reaction is completed, the mixture is washed with deionized water and dried at room temperature to obtain PHEMA hydrogel.

[0043] Based on the above formulation, the cross-linking with boric acid, combined with ortho-diolized mesoporous silica, significantly increases the hydrophilicity and water content of the hydrogel. Secondly, the increased number of hydroxyl groups enhances the bonding strength between the hydrogel and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, further improving the hydrogel's water content and promoting the formation of uniform pores, thus achieving a balance between optical transparency and oxygen permeability. Furthermore, it also imparts drug delivery properties to the hydrogel.

[0044] The beneficial effects of this invention are:

[0045] (1) In the technical solution of the present invention, boric acid is used as a crosslinking agent, which can introduce a large number of hydroxyl groups in the hydrogel matrix, thereby increasing the water content of the hydrogel. In addition, boric acid, as an antibacterial and antifungal agent, has broad-spectrum antibacterial properties against bacteria, yeast and fungi. Furthermore, the added hydroxyl groups can interact better with [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, which is beneficial to the binding of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide.

[0046] (2) In the technical solution of the present invention, the addition of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide can enhance biocompatibility and antifouling performance, and can also adjust the water content and pore size of the hydrogel, thereby balancing optical transparency and oxygen permeability.

[0047] (3) In the technical solution of the present invention, by depositing polydopamine on the surface of mesoporous silica, amino and benzoquinone functional groups are introduced on the surface of mesoporous silica. The introduced amino functional groups can better adsorb hyaluronic acid, so as to achieve continuous drug delivery to the eyes. The introduced benzoquinone functional groups can combine with branched polyethyleneimine through Schiff base reaction. The mesoporous silica with branched polyethyleneimine is then combined with glycidyl to achieve the introduction of vicinal diol. The introduced vicinal diol is dispersed in the hydrogel matrix with the mesoporous silica, which improves the oxygen permeability and water content of the hydrogel. In addition, vicinal diol can better combine with boron element to achieve stable dispersion of nanoparticles and improve the stability of hydrogel. Attached Figure Description

[0048] Figure 1 This is the reaction equation for branched polyethyleneimine and glycidol according to the present invention;

[0049] Figure 2 It is the chemical equation for the synthesis of the sustained-release agent. Detailed Implementation

[0050] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0051] Preparation Example 1

[0052] The sustained-release agent is prepared by the following steps:

[0053] 72.6 mL of cyclohexane, 17.64 mL of isooctyl alcohol, 16.87 mL of Triton X-100 and 15 mg of CTAB were mixed and stirred for 30 minutes to form a transparent microemulsion. 10 μL of APTES dissolved in 4 mL of deionized water was added to the microemulsion. The mixture was stirred for 10 minutes and then sonicated for 30 minutes to form a homogeneous solution.

[0054] 640 μL of TEOS, 370 μL of TMAPS and 800 μL of ammonia were added dropwise to the solution and stirred for 24 hours. After adding 40 mL of acetone, the mixture was centrifuged at 8000 rpm for 10 minutes. The obtained nanoparticles were washed sequentially with ethanol, ultrapure water, glacial acetic acid and deionized water, and then freeze-dried to obtain nanoporous silica (average pore size 30 nm).

[0055] 1 g of nanoporous silica was added to 100 mL of 10 mmol / L Tris buffer solution (pH 8.5) and ultrasonically dispersed for 1 h. Then, 0.2 g of dopamine hydrochloride was added to the solution and magnetically stirred at room temperature for 24 h. After the reaction was completed, the mixture was centrifuged for 20 min and washed three times with ethanol to remove unreacted monomers. The resulting solid was placed in an oven and dried at 170 °C for 12 h to obtain polydopamine-modified silica.

[0056] 0.1 g of polydopamine-modified silica was dispersed in 10 mL of 10 mmol / L Tris buffer (pH 8.5), and 5 mL of hyaluronic acid (eye drop grade, Mw = 3 kDa) was added to the solution. The mixture was stirred for 5 minutes at room temperature in the dark, and then centrifuged at 20,000 rpm for 20 minutes. The supernatant was removed, the precipitate was washed three times with deionized water, and then freeze-dried to obtain polydopamine-modified drug-loaded silica.

[0057] 1g of polydopamine-modified drug-loaded silica and 2g of branched polyethyleneimine (Mn = 10000g / mol) were placed in an autoclave, 70mL of deionized water was added, the autoclave was sealed, and heated in a vacuum oven at 145℃ for 6.5 hours. After cooling, they were repeatedly washed with water at 60-70℃ until the rinsing solution became neutral. Then they were dried under vacuum at 50℃ for 24 hours to obtain branched polydopamine-modified drug-loaded silica.

[0058] 10 mg of branched polydopamine-modified drug-loaded silica was dispersed in 0.5 mL of glycidyl ether and 50 mL of ethanol, and refluxed continuously in an oil bath at 80 °C for 24 hours. Then, it was taken out and washed several times with deionized water, and vacuum dried at 45 °C to obtain a sustained-release agent.

[0059] Preparation Example 2

[0060] 72.6 mL of cyclohexane, 17.64 mL of isooctyl alcohol, 16.87 mL of Triton X-100 and 15 mg of CTAB were mixed and stirred for 30 minutes to form a transparent microemulsion. 10 μL of APTES dissolved in 4 mL of deionized water was added to the microemulsion. The mixture was stirred for 10 minutes and then sonicated for 30 minutes to form a homogeneous solution.

[0061] 640 μL TEOS, 370 μL TMAPS and 800 μL ammonia were added dropwise to the solution and stirred for 24 hours. 40 mL of acetone was added and the mixture was centrifuged at 8000 rpm for 10 minutes. The obtained nanoparticles were washed sequentially with ethanol, ultrapure water, glacial acetic acid and deionized water and then freeze-dried to obtain nanoporous silica.

[0062] 1 g of nanoporous silica was added to 100 mL of 10 mmol / L Tris buffer solution (pH 8.5) and ultrasonically dispersed for 1 h. Then, 0.2 g of dopamine hydrochloride was added to the solution and magnetically stirred at room temperature for 24 h. After the reaction was completed, the mixture was centrifuged for 20 min and washed three times with ethanol to remove unreacted monomers. The resulting solid was placed in an oven and dried at 170 °C for 12 h to obtain polydopamine-modified silica.

[0063] 0.1 g of polydopamine-modified silica was dispersed in 10 mL of 10 mmol / L Tris buffer (pH 8.5), and 5 mL of hyaluronic acid was added to the solution. The mixture was stirred for 5 minutes at room temperature in the dark, and then centrifuged at 20,000 rpm for 20 minutes. The supernatant was removed, and the precipitate was washed three times with deionized water. After freeze-drying, polydopamine-modified drug-loaded silica, i.e., the sustained-release agent, was obtained.

[0064] Preparation Example 3

[0065] The sustained-release agent is prepared by the following steps:

[0066] 72.6 mL of cyclohexane, 17.64 mL of isooctyl alcohol, 16.87 mL of Triton X-100 and 15 mg of CTAB were mixed and stirred for 30 minutes to form a transparent microemulsion. 10 μL of APTES dissolved in 4 mL of deionized water was added to the microemulsion. The mixture was stirred for 10 minutes and then sonicated for 30 minutes to form a homogeneous solution.

[0067] 640 μL TEOS, 370 μL TMAPS and 800 μL ammonia were added dropwise to the solution and stirred for 24 hours. 40 mL of acetone was added and the mixture was centrifuged at 8000 rpm for 10 minutes. The obtained nanoparticles were washed sequentially with ethanol, ultrapure water, glacial acetic acid and deionized water and then freeze-dried to obtain nanoporous silica.

[0068] 1 g of nanoporous silica was added to 100 mL of 10 mmol / L Tris buffer solution (pH 8.5) and ultrasonically dispersed for 1 h. Then, 0.2 g of dopamine hydrochloride was added to the solution and magnetically stirred at room temperature for 24 h. After the reaction was completed, the mixture was centrifuged for 20 min and washed three times with ethanol to remove unreacted monomers. The resulting solid was placed in an oven and dried at 170 °C for 12 h to obtain polydopamine-modified silica.

[0069] 0.1 g of polydopamine-modified silica was dispersed in 10 mL of 10 mmol / L Tris buffer (pH 8.5), and 5 mL of hyaluronic acid was added to the solution. The mixture was stirred for 5 minutes at room temperature in the dark, and then centrifuged at 20,000 rpm for 20 minutes. The supernatant was removed, the precipitate was washed three times with deionized water, and then freeze-dried to obtain polydopamine-modified drug-loaded silica.

[0070] 1g of polydopamine-modified drug-loaded silica and 2g of branched polyethyleneimine were placed in an autoclave, 70mL of deionized water was added, the autoclave was sealed, and heated in a vacuum oven at 145℃ for 6.5 hours. After cooling, the silica was repeatedly washed with water at 60-70℃ until the rinse solution became neutral. Then, the silica was dried under vacuum at 50℃ for 24 hours to obtain branched polydopamine-modified drug-loaded silica, i.e., the sustained-release agent.

[0071] Example 1

[0072] A PHEMA hydrogel comprises the following raw materials in parts by weight: 40 parts of 2-hydroxyethyl methacrylate, 30 parts of reinforcing agent ([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide), 20 parts of solvent (deionized water), 1 part of crosslinking agent (boric acid), 0.5 parts of initiator and 1 part of the sustained-release agent prepared in Preparation Example 1;

[0073] The preparation method includes the following steps:

[0074] S1. Weigh out the raw materials according to the formula mass;

[0075] S2. The crosslinking agent is dispersed in 2-hydroxyethyl methacrylate and stirred continuously at room temperature for 15 min. Then, the reinforcing agent and the slow-release agent are dispersed in the solvent and sonicated for 20 min. Subsequently, the initiator is added dropwise to the system and the reaction is refluxed at 80°C under magnetic stirring for 3 hours. After the reaction is completed, the mixture is washed with deionized water and dried at room temperature to obtain PHEMA hydrogel.

[0076] Example 2

[0077] The difference between this embodiment and Embodiment 1 is that:

[0078] A PHEMA hydrogel comprises the following raw materials in parts by weight: 45 parts 2-hydroxyethyl methacrylate, 35 parts reinforcing agent ([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide), 25 parts solvent (deionized water), 1.5 parts crosslinking agent (boric acid), 0.8 parts initiator (potassium persulfate), and 1.5 parts sustained-release agent prepared in Preparation Example 1; the remaining steps are carried out concurrently with those in Example 2.

[0079] Example 3

[0080] The difference between this embodiment and Embodiment 1 is that:

[0081] A PHEMA hydrogel comprises the following raw materials in parts by weight: 50 parts of 2-hydroxyethyl methacrylate, 40 parts of reinforcing agent ([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide), 30 parts of solvent (deionized water), 2 parts of crosslinking agent (boric acid), 1 part of initiator and 2 parts of sustained-release agent prepared in Preparation Example 1;

[0082] Comparative Example 1

[0083] A PHEMA hydrogel comprises the following raw materials in parts by weight: 40 parts of 2-hydroxyethyl methacrylate, 30 parts of reinforcing agent ([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide), 20 parts of solvent (deionized water), 1 part of crosslinking agent (boric acid), 0.5 parts of initiator and 1 part of sustained-release agent prepared in Preparation Example 2.

[0084] Preparation process in sync with Example 1.

[0085] Comparative Example 2

[0086] A PHEMA hydrogel comprises the following raw materials in parts by weight: 40 parts of 2-hydroxyethyl methacrylate, 30 parts of reinforcing agent ([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide), 20 parts of solvent (deionized water), 1 part of crosslinking agent (boric acid), 0.5 parts of initiator and 1 part of sustained-release agent prepared in Preparation Example 3.

[0087] Preparation process in sync with Example 1.

[0088] Comparative Example 3

[0089] A PHEMA hydrogel comprises the following raw materials in parts by weight: 40 parts of 2-hydroxyethyl methacrylate, 30 parts of reinforcing agent ([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide), 20 parts of solvent (deionized water), 0.5 parts of initiator and 1 part of sustained-release agent prepared in Preparation Example 1.

[0090] Comparative Example 4

[0091] A PHEMA hydrogel comprises the following raw materials in parts by weight: 40 parts of 2-hydroxyethyl methacrylate, 20 parts of solvent (deionized water), 1 part of crosslinking agent (boric acid), 0.5 parts of initiator, and 1 part of sustained-release agent prepared in Preparation Example 3.

[0092] Preparation process in sync with Example 1.

[0093] The performance of the PHEMA hydrogels prepared in Examples 1-3 and Comparative Examples 1-4 was then tested:

[0094] T1, Equilibrium Moisture Content (EWC) Test:

[0095] Cut the hydrogel into disc shapes (2 cm in diameter, 3 mm thick) with a blade, and dry the discs overnight in a vacuum oven at 50°C. After drying, carefully weigh the hydrogel discs and record the weight (Wi). Then, place the hydrogel discs in 3 mL of PBS solution (pH 7.4) at 34°C (physiological corneal temperature) and allow them to swell for 24 hours. After reaching equilibrium, remove the surface water with soft paper and immediately record the weight (Ws). The swelling rate was calculated by gravimetric analysis using the following formula, and the experiment was repeated three times.

[0096] Equilibrium moisture content (%) = (Ws - Wi) / Ws × 100

[0097] T2, Refractive Index Measurement:

[0098] The refractive index (RI) of the hydrogel was measured using a refractometer (Atago, Bellevue, Washington), with all measurements performed in triplicate. The optical transmittance of the hydrogel, fully swollen with deionized water, was measured using a UV-1600 UV-Vis spectrophotometer (Shimadzu, Japan) in the wavelength range of 200–800 nm. Measurements were taken with the hydrogel inserted into one side of a disposable cuvette. UV-Vis light was applied directly to the sample surface. All transparency measurements were taken at room temperature.

[0099] T3, Oxygen permeability measurement:

[0100] The content of the mixed hydrogel (artificially manufactured, 201T oxygen permeameter) was determined by an oxygen permeation analyzer using AC polarography.

[0101] T4. Anti-fouling test:

[0102] The adsorption of IGG protein on the hydrogel was determined by enzyme-linked immunosorbent assay (ELISA).

[0103] The test results are shown in Table 1 below:

[0104] Table 1

[0105]

[0106]

[0107] As shown in Table 1 above, using boric acid as a linker between 2-hydroxyethyl methacrylate and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide greatly increases the equilibrium water content of the 2-hydroxyethyl methacrylate hydrogel.

[0108] The addition of boric acid enabled a better bond between [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide and the hydrogel, improving the hydrogel's transparency, biocompatibility, self-antibacterial properties, and antifouling performance.

[0109] HA / PBS solutions with different pH values ​​were fixed at 0.1 wt%, and 3 mL of each solution was absorbed to obtain the standard sample. The test results are shown in Table 2 below.

[0110] Table 2

[0111]

[0112]

[0113] Table 2 above shows that silica with added branched polydopamine can better achieve HA loading and release. It can also be seen from Example 1 and Comparative Example 2 that the addition of vicinal diol has little effect on HA loading and release.

[0114] The above description is merely an example and illustration of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described, or use similar methods to replace them, as long as they do not deviate from the invention or exceed the scope defined in the claims, all of which should fall within the protection scope of the present invention.

Claims

1. A PHEMA hydrogel, characterized by: It includes the following raw materials by weight: 40-50 parts 2-hydroxyethyl methacrylate, 30-40 parts reinforcing agent, 20-30 parts solvent, 1-2 parts crosslinking agent, 0.5-1 part initiator and 1-2 parts sustained-release agent; The reinforcing agent is the zwitterionic compound [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide; The sustained-release agent is prepared by the following steps: A1. Place the drug-loaded silica modified with polydopamine and branched polyethyleneimine into an autoclave, add deionized water, seal the autoclave, heat in a vacuum oven at 145°C for 6.5 hours, cool, and wash repeatedly with water at 60-70°C until the rinsing solution becomes neutral. Then dry under vacuum at 50°C for 24 hours to obtain the drug-loaded silica modified with polydopamine. A2. The branched polydopamine-modified drug-loaded silica was dispersed in glycidyl ether and ethanol, refluxed in an oil bath at 80°C for 24 hours, removed and washed several times with deionized water, and dried under vacuum at 45°C to obtain a sustained-release agent. Polydopamine-modified drug-loaded silica is prepared by the following steps: B1. Add nanoporous silica to 10 mmol / L Tris buffer solution at pH 8.5 and sonicate for 1 h. Add dopamine hydrochloride to the solution and stir magnetically at room temperature for 24 h. After the reaction is complete, centrifuge the mixture for 20 min, wash with ethanol 3 times to remove unreacted monomers, and place the solid in an oven to dry at 170 °C for 12 h to obtain polydopamine-modified silica. B2. Disperse polydopamine-modified silica in 10 mmol / L Tris buffer at pH 8.5, add hyaluronic acid, stir at room temperature in the dark for 5 minutes, centrifuge at 20,000 rpm for 20 minutes, remove the supernatant, wash the precipitate three times with deionized water, and freeze-dry to obtain polydopamine-modified drug-loaded silica. Nanoporous silica is prepared by the following steps: C1. Mix cyclohexane, isooctyl alcohol, Triton X-100 and CTAB and stir for 30 minutes to form a transparent microemulsion. Add APTES dissolved in deionized water to the microemulsion, stir for 10 minutes, and sonicate for 30 minutes to form a homogeneous solution. C2. TEOS, TMAPS and ammonia were added dropwise to the solution and stirred for 24 hours. Acetone was added and the mixture was centrifuged at 8000 rpm for 10 minutes. The obtained nanoparticles were washed sequentially with ethanol, ultrapure water, glacial acetic acid and deionized water, and then freeze-dried to obtain nanoporous silica. The crosslinking agent is boric acid.

2. The PHEMA hydrogel according to claim 1, characterized in that: The mass ratio of polydopamine-modified drug-loaded silica, branched polyethyleneimine, and deionized water was 1:2:

70. The ratio of branched polydopamine-modified drug-loaded silica, glycidyl ether, and ethanol was 10 mg: 0.5 mL: 50 mL.

3. The PHEMA hydrogel according to claim 1, wherein: The ratio of nanoporous silica, Tris-HCl buffer, and dopamine hydrochloride was 1 g: 100 mL: 0.2 g. The ratio of polydopamine-modified silica, Tris buffer, and hyaluronic acid was 0.1 g: 10 mL: 5 mL.

4. The PHEMA hydrogel of claim 1, wherein: The volume ratio of cyclohexane, isooctyl alcohol, Triton X-100, CTAB, deionized water, and APTES was 72.6 mL: 17.64 mL: 16.87 mL: 15 mg: 4 mL: 10 μL; The ratio of TEOS, TMAPS, ammonia, and acetone used is 640 μL: 370 μL: 800 μL: 40 mL.

5. The PHEMA hydrogel of claim 1, wherein: The solvent is deionized water, and the initiator is potassium persulfate.

6. A method for preparing a PHEMA hydrogel as described in any one of claims 1-5, characterized in that: Includes the following steps: S1. Weigh out the raw materials according to the formula mass; S2. The crosslinking agent is dispersed in 2-hydroxyethyl methacrylate and stirred continuously at room temperature for 15 min. Then, the reinforcing agent and the slow-release agent are dispersed in the solvent and sonicated for 20 min. Subsequently, the initiator is added dropwise to the system and the reaction is refluxed at 80°C under magnetic stirring for 3 hours. After the reaction is completed, the mixture is washed with deionized water and dried at room temperature to obtain PHEMA hydrogel.

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