A high-toughness hydrogel for use as an extraocular muscle and a method for preparing and using the same

Abstract

The application relates to a high-toughness hydrogel artificial muscle used as an extraocular muscle and a preparation method and application thereof, and belongs to the field of biomedical materials. The composite hydrogel is composed of gelatin, N-isopropyl acrylamide, tannic acid (TA), MXene (Ti3C2T x ), and a glycerin / water mixed dispersant. A double-network polymer skeleton constructed by using gelatin and N-isopropyl acrylamide provides good mechanical properties for the gel and good biocompatibility. By introducing natural polyphenol tannic acid into the polymer network, the hydrogel has good biocompatibility by using the antibacterial property and the antioxidant property. A large number of o-diphenol and o-benzene triol in the tannic acid molecules can form hydrogen bonds with the polymer molecular chains, thereby enhancing the tensile property of the gel. The prepared hydrogel has good stretchability, antioxidant property, antibacterial property, tissue adhesion and electrical property, so that the hydrogel can be used as an artificial muscle material and used as an artificial extraocular muscle.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials, specifically relating to a high-strength and tough hydrogel used as an extraocular muscle, its preparation method, and its application. Background Technology

[0002] Hydrogel-based artificial muscles hold immense promise for applications in soft robotics, prosthetic implantation, and biomedical engineering. While traditional hydrogels possess a high water content network and basic biocompatibility similar to natural tissues, their inherent mechanical strength and toughness are low, and they lack dynamic response to external signals, limiting their application in precision biomimetic actuation. Achieving reliable artificial muscle replacement and controllable actuation functions in complex physiological environments remains a significant challenge.

[0003] Extraocular muscles, as key structures controlling eye movement, maintaining binocular vision, and enabling precise visual tracking, play a vital role in ensuring normal visual function and interactive perception. However, these delicate extraocular muscles are highly susceptible to damage from trauma, neuropathy, or thyroid-associated eye diseases. To address various eye movement disorders, surgical correction or implantation of substitutes has become the mainstream treatment. Traditional implant materials, such as silicone and porous polymers, not only lack the elasticity and active actuation capabilities of natural muscles, failing to perfectly simulate complex biomechanical contractions, but also often suffer from poor tissue compatibility. This can easily cause mechanical friction, immune rejection, and secondary damage to the delicate surrounding ocular tissues, leading to stiff eye movement and slow postoperative recovery.

[0004] The poor mechanical load-bearing capacity, weak responsive driving force, and insufficient cell affinity in the long-term in vivo environment exhibited by traditional flexible biomimetic materials are the main obstacles to their application in the field of ophthalmic artificial muscles. To effectively simulate the long-term, high-frequency, and multi-dimensional contraction and relaxation movements of natural extraocular muscles, artificial muscle materials must possess both extremely high biocompatibility and excellent strength and toughness to resist mechanical fatigue. Furthermore, endowing the material with actuability similar to the nerve innervation of natural muscles is key to achieving dynamic biomimetic functions.

[0005] Therefore, developing a hydrogel artificial muscle that integrates excellent biocompatibility, high strength, high toughness, and superior actuation capability can meet the requirements for real-time dynamic mechanical response and active actuation in complex ocular movement scenarios. This not only effectively avoids foreign body rejection after implantation and promotes the precise reconstruction of extraocular muscle physiological function, but also provides a solid research foundation for integrating soft actuators with precise ocular tissue repair, which has profound significance for the development of multifunctional biomimetic materials in the fields of ophthalmic medical devices and intelligent artificial organs. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of hydrogel materials as artificial muscle materials, such as poor mechanical properties, lack of antibacterial properties, and easy oxidation, and to provide a high-strength and tough hydrogel for use as extraocular muscle, its preparation method, and its applications. The prepared composite hydrogel has good mechanical tensile properties and good biocompatibility, and has broad application prospects in artificial muscles, wearable devices, and biomedicine.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] A method for preparing a high-strength, tough hydrogel for use as extraocular muscle, the method comprising:

[0009] Step 1: At 45℃, mix gelatin and water at a mass ratio of 1:9 and stir evenly for 3-5 hours to form a homogeneous solution.

[0010] Step 2: Add MXene to the above mixture and continue stirring until homogeneous;

[0011] Step 3: At 25~30℃, N-isopropylacrylamide and water are mixed at a mass ratio of 1:9 and stirred until homogeneous to form an N-isopropylacrylamide solution;

[0012] Step 4: Add the solution from Step 3 to the solution from Step 2 at a volume ratio of 1:1 and mix and stir for 1 to 6 hours;

[0013] Step 5: Add the solution from Step 4 into the polytetrafluoroethylene mold, then perform low-temperature polymerization and allow the gel block to air dry until all moisture evaporates;

[0014] Step 6: Add tannic acid powder to water and stir until a 10wt%~20wt% tannic acid aqueous solution is formed;

[0015] Step 7: Mix the solution obtained in Step 6 with glycerin at a volume ratio of 1:1 to 2 and stir until homogeneous to form a uniform solution;

[0016] Step 8: At 25~30℃, immerse the dried hydrogel film from Step 5 in the solution from Step 7 for 6~12 hours to allow it to fully absorb the glycerol / water mixed dispersant. The glycerol aqueous solution enables the gel to retain water, thus achieving a water-locking effect in the air.

[0017] Furthermore, in step two, MXene is obtained by selectively etching Al atomic layers using an HCl-LiF system according to a modified Mild method, resulting in nanosheets with an average size of 300~500nm and a thickness of 1.6nm.

[0018] Furthermore, in step two, the concentration of MXene in the prepared dispersion is 1~3 mg / ml.

[0019] Furthermore, in step five, the low-temperature polymerization temperature is 25°C, and the time is 6~10h.

[0020] A high-strength and tough hydrogel prepared by the above preparation method is used as an extraocular muscle.

[0021] The high-strength and tough hydrogel prepared by the above method is used as an artificial muscle.

[0022] Compared with existing technologies, the present invention has the following advantages:

[0023] 1. Gelatin, as a natural polymer, is abundant, readily available, green, non-toxic, and has good cell affinity and excellent mechanical properties; tannic acid, as a natural plant polyphenol, has good antibacterial properties and can solve problems in biomedicine.

[0024] 2. The hydrogel prepared by this invention has higher tensile strength and toughness, can resist deformation, and is comparable to the strength of artificial muscle.

[0025] 3. The introduction of tannic acid not only enhances the strength and toughness of the gel, but also endows the hydrogel with excellent antioxidant, antibacterial and biocompatibility. Attached Figure Description

[0026] Figure 1 Flowchart of a method for preparing a high-strength, tough hydrogel artificial muscle for use as extraocular muscle.

[0027] Figure 2 This is an experimental diagram of biological adhesion of a high-strength and tough hydrogel artificial muscle used as an extraocular muscle;

[0028] Figure 3 The images are infrared spectra, stress-strain curves, sample diagrams, toughness bar charts, tensile strength bar charts, and SEM images of the hydrogels of Examples 1(a), 2(b), and 3(c). Detailed Implementation

[0029] The technical solution of the present invention will be further described below with reference to the embodiments, but it is not limited thereto. Any modifications or equivalent substitutions to the technical solution of the present invention without departing from the spirit and scope of the technical solution of the present invention should be covered within the protection scope of the present invention.

[0030] In this invention, a dual-network polymer backbone constructed from gelatin and N-isopropylacrylamide provides the gel with excellent mechanical properties and good biocompatibility. By introducing natural polyphenols, tannins, into the polymer network, their antibacterial and antioxidant properties enhance the hydrogel's biocompatibility. The abundant catechols and pyrogallols in the tannin molecules can form hydrogen bonds with the polymer molecular chains, enhancing the gel's stretchability. Furthermore, the introduction of the two-dimensional nanomaterial MXene endows the gel with excellent conductivity, enabling the stable conversion of human motion signals into real-time monitorable electrical signals. The prepared hydrogel exhibits good stretchability, antioxidant properties, antibacterial properties, tissue adhesion, and electrical properties, allowing for real-time monitoring of artificial muscle movements.

[0031] Example 1:

[0032] Step 1: At 45℃, mix gelatin and water in a mass ratio of 1:9 and stir evenly for 3 hours to form a homogeneous solution;

[0033] Step 2: Add MXene (1 mg / ml) to the above mixture and continue to stir evenly. MXene is obtained by selectively etching Al atomic layers using the HCl-LiF system according to the modified Mild method. The average size of the nanosheets is 300~500 nm and the thickness is 1.6 nm. The concentration of MXene in the prepared dispersion is 1 mg / ml.

[0034] Step 3: At room temperature, mix N-isopropylacrylamide and water in a mass ratio of 1:9 and stir until homogeneous to form an N-isopropylacrylamide solution;

[0035] Step 4: Add the solution from Step 3 to the solution from Step 2 at a volume ratio of 1:1 and mix and stir for 4 hours;

[0036] Step 5: Add the solution from Step 4 into the polytetrafluoroethylene mold, and then carry out low-temperature polymerization (room temperature 25℃, polymerization for 6 hours). After polymerization, ventilate and dry the gel block until all moisture evaporates.

[0037] Step 6: Add tannic acid powder to water and stir until evenly mixed to form a 15% (w / w) tannic acid aqueous solution;

[0038] Step 7: Mix the solution obtained in Step 6 with glycerin at a ratio of 1:1.5 and stir until homogeneous to form a uniform solution;

[0039] Step 8: At room temperature, the dried hydrogel film from Step 5 is immersed in the solution from Step 7 for 8 hours to allow it to fully absorb the glycerol / water mixed dispersant. The resulting hydrogel has a strength of 1.36 ± 0.25 MPa and a toughness of 1.84 ± 0.35 MJ / m. 3At 70% tensile strain, gf = 0.6~1.0.

[0040] Example 2:

[0041] Step 1: At 45℃, mix gelatin and water in a mass ratio of 1:9 and stir evenly for 4 hours to form a homogeneous solution;

[0042] Step 2: Add MXene (2 mg / ml) to the above mixture and continue to stir evenly. MXene is obtained by selectively etching Al atomic layers using the HCl-LiF system according to the modified Mild method. The average size of the nanosheets is 300~500 nm and the thickness is 1.6 nm. The concentration of MXene in the prepared dispersion is 2 mg / ml.

[0043] Step 3: At room temperature, mix N-isopropylacrylamide and water in a mass ratio of 1:9 and stir until homogeneous to form an N-isopropylacrylamide solution;

[0044] Step 4: Add the solution from Step 3 to the solution from Step 2 at a volume ratio of 1:1 and mix for 4 hours;

[0045] Step 5: Add the solution from Step 4 into the polytetrafluoroethylene mold, and then carry out low-temperature polymerization (room temperature 25℃, polymerization for 6 hours). After polymerization, ventilate and dry the gel block until all moisture evaporates.

[0046] Step 6: Add tannic acid powder to water and stir until evenly mixed to form a tannic acid aqueous solution with a mass fraction of 12%;

[0047] Step 7: Mix the solution obtained in Step 6 with glycerin in a 1:1 ratio and stir until homogeneous;

[0048] Step 8: At room temperature, the dried hydrogel film from Step 5 is immersed in the solution from Step 7 for 10 hours to allow it to fully absorb the glycerol / water mixed dispersant. The resulting hydrogel has a strength of 2.23 ± 0.34 MPa and a toughness of 3.19 ± 0.25 MJ / m. 3 At 70% tensile strain, gf = 0.8~1.2.

[0049] Example 3:

[0050] Step 1: At 45℃, mix gelatin and water in a mass ratio of 1:9 and stir evenly for 5 hours to form a homogeneous solution;

[0051] Step 2: Add MXene (3 mg / ml) to the above mixture and continue to stir evenly. MXene is obtained by selectively etching Al atomic layers using the HCl-LiF system according to the modified Mild method. The average size of the nanosheets is 300~500 nm and the thickness is 1.6 nm. The concentration of MXene in the prepared dispersion is 3 mg / ml.

[0052] Step 3: At room temperature, mix N-isopropylacrylamide and water in a mass ratio of 1:9 and stir until homogeneous to form an N-isopropylacrylamide solution;

[0053] Step 4: Add the solution from Step 3 to the solution from Step 2 at a volume ratio of 1:1 and mix for 6 hours;

[0054] Step 5: Add the solution from Step 4 into the polytetrafluoroethylene mold, and then carry out low-temperature polymerization (room temperature 25℃, polymerization for 6 hours). After polymerization, ventilate and dry the gel block until all moisture evaporates.

[0055] Step 6: Add tannic acid powder to water and stir until evenly mixed to form a 20% tannic acid aqueous solution;

[0056] Step 7: Mix the solution obtained in Step 6 with glycerin in a 1:2 ratio and stir until homogeneous;

[0057] Step 8: At room temperature, the dried hydrogel film from Step 5 is immersed in the solution from Step 7 for 12 hours to allow it to fully absorb the glycerol / water mixed dispersant. The resulting hydrogel has a strength of 1.93 ± 0.32 MPa and a toughness of 1.96 ± 0.28 MJ / m. 3 At 70% tensile strain, gf = 0.6~0.8.

[0058] Figure 1 A technical roadmap for preparing hydrogels for use as extraocular muscles. Figure 2 This is a schematic diagram illustrating the use of this hydrogel in biological experiments. Figure 3 This demonstrates the successful synthesis of the hydrogel and the successful introduction of MXene nanosheets. Figure 3 b, c, e, f demonstrate that the hydrogel possesses excellent mechanical properties. Figure 3 GSM10, GSM20, and GSM30 were obtained through Examples 1, 2, and 3, respectively. GS served as the blank control group, and GSMN20 served as the blank control group for Example 2. The addition of MXene enabled the hydrogel to acquire good mechanical properties, with the GSM20 hydrogel obtained in Example 2 exhibiting the highest strength and toughness. Figure 3g\h\i represent the internal structures of the hydrogels under GSM10, GSM20, and GSM30 scanning electron microscopes in Examples 1, 2, and 3, respectively. The arrangement of MXene nanosheets inside the hydrogels can be observed. In Example 2, the MXene nanosheets of GSM20 are clearly layered and tightly stacked, resulting in the best mechanical properties.

Claims

1. A method for preparing a high-strength, tough hydrogel for use as extraocular muscle, characterized in that: The method is as follows: Step 1: At 45℃, mix gelatin and water at a mass ratio of 1:9 and stir evenly for 3-5 hours to form a homogeneous solution. Step 2: Add MXene to the above mixture and continue stirring until homogeneous; Step 3: At 25~30℃, N-isopropylacrylamide and water are mixed at a mass ratio of 1:9 and stirred until homogeneous to form an N-isopropylacrylamide solution; Step 4: Add the solution from Step 3 to the solution from Step 2 at a volume ratio of 1:1 and mix and stir for 1 to 6 hours; Step 5: Add the solution from Step 4 into the polytetrafluoroethylene mold, then perform low-temperature polymerization and allow the gel block to air dry until all moisture evaporates; Step 6: Add tannic acid powder to water and stir until a 10wt%~20wt% tannic acid aqueous solution is formed; Step 7: Mix the solution obtained in Step 6 with glycerin at a volume ratio of 1:1 to 2 and stir until homogeneous to form a uniform solution; Step 8: At 25~30℃, add the dried hydrogel film from Step 5 into the solution from Step 7 and soak for 6~12 hours to allow it to fully absorb the glycerol / water mixed dispersant.

2. The method for preparing a high-strength, tough hydrogel artificial muscle for use as an extraocular muscle according to claim 1, characterized in that: In step two, MXene is obtained by selectively etching Al atomic layers using an HCl-LiF system according to a modified Mild method, resulting in nanosheets with an average size of 300~500nm and a thickness of 1.6nm.

3. The method for preparing a high-strength, tough hydrogel artificial muscle for use as an extraocular muscle according to claim 1, characterized in that: In step two, the concentration of MXene in the prepared dispersion is 1~3 mg / ml.

4. The method for preparing a high-strength, tough hydrogel artificial muscle for use as an extraocular muscle according to claim 1, characterized in that: In step five, the low-temperature polymerization temperature is 25℃, and the time is 6~10h.

5. A high-strength and tough hydrogel prepared by the preparation method according to any one of claims 1 to 4, which can be used as an extraocular muscle.

6. The application of a high-strength and tough hydrogel prepared by the preparation method according to any one of claims 1 to 4 as an artificial muscle.

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