Fluorescent traceable hydrogel material for sealing retinal fissure as well as preparation method and application of fluorescent traceable hydrogel material

Abstract

The invention discloses a hydrogel material used for sealing retinal fissure and capable of realizing fluorescence tracing as well as a preparation method and application of the hydrogel material. The hydrogel material comprises four-arm polyethylene glycol-maleimide, four-arm polyethylene glycol-mercaptan and fluorescein-maleimide, according to the hydrogel material, four-arm polyethylene glycol-maleimide, four-arm polyethylene glycol-thiol and fluorescein are subjected to crosslinking, and then a four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol / fluorescein compound is obtained. The four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol / fluorescein chemically-crosslinked retinal crack sealing material disclosed by the invention has a relatively good sealing effect, is low in biotoxicity, good in biocompatibility and safe to use, and meets the requirements of being applied to pore-derived retinal detachment treatment.

Description

Technical Field

[0001] The present invention relates to the field of biomaterial technology and medical product technology, and in particular to a hydrogel material capable of fluorescent tracing for sealing retinal holes, and a preparation method and application thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance some understanding of the overall background of the invention and should not be necessarily regarded as an admission or any form of suggestion that the information constitutes the prior art already known to those skilled in the art.

[0003] Rhegmatogenous retinal detachment is one of the most common retinal diseases, with an annual incidence of 6.3 to 17.9 cases per 100,000 people. Rhegmatogenous retinal detachment can lead to dramatic vision loss, photoreceptor cell degeneration, retinal nerve fiber layer damage, and complications such as proliferative vitreoretinopathy. The necessary factors for the development of rhegmatogenous retinal detachment are retinal break formation, vitreous traction, and liquefaction. The most important principle of treatment is closure of the retinal break.

[0004] Current surgical treatment options include pars plana vitrectomy, scleral buckling, pneumatic retinopexy, and combinations of these procedures. With the continuous advancement of surgical techniques and instruments in recent years, pars plana vitrectomy has become the most widely used treatment for rhegmatogenous retinal detachment. However, postoperatively, it often requires prolonged maintenance of a specific position (such as the prone position) to optimize the support of the filler, which poses potential risks for patients with comorbid spinal or cardiovascular diseases. Furthermore, complications such as silicone oil emulsification, lens metabolic disorders, and retinal toxicity are unavoidable, impacting patients' postoperative quality of life. The selection of scleral buckling and pneumatic retinopexy procedures requires specific requirements for the location, number, morphology, and vitreous status of the retinal breaks, limiting their widespread clinical use. Therefore, the development of simpler, more effective, and safer treatment options for RRD is of great clinical significance. Currently, sealing retinal breaks with retinal sealants is considered a promising new treatment option.

[0005] Currently, retinal sealants used in ophthalmic surgery fall into two main categories: sealants based on natural compounds (such as protein derivatives and polysaccharide derivatives) and sealants based on synthetic materials (such as cyanoacrylates and polyethylene glycol derivatives). However, many biomaterials are limited in their use within the intraocular environment due to their slow gelation and demanding gelation conditions. These materials pose the risk of incomplete coverage of retinal tears and even leakage into the subretinal space. Furthermore, most sealants are colorless and transparent, presenting numerous challenges in visibility during operation. Furthermore, most retinal sealants require post-vitrectomy application.

[0006] The vitreous humor is a transparent, jelly-like substance that occupies four-fifths of the intraocular space. It supports and protects the retina and the eyeball wall, maintaining adhesion between the retina and the choroid. Its presence protects the retina from flattening. The presence of the vitreous humor precludes complex intraocular procedures (such as unfolding gel sheets, using light or temperature-controlled devices to promote sealant cross-linking), and its jelly-like, semisolid nature may impair the function of some sealants. Therefore, a vitrectomy is required before application of the sealant. The challenge lies in finding a material that can perform its sealing function within the vitreous environment with simple manipulation to seal retinal tears.

[0007] While many materials are currently being used in retinal break research, visibility remains a challenge. Without visibility, it is difficult to assess the completeness of the retinal break seal under a microscope, and it is also difficult to assess the effectiveness of the treatment after surgery. The key to solving this problem lies in finding a method to observe transparent retinal sealing materials. This method involves improving the material itself or the surgical and inspection equipment. Summary of the Invention

[0008] In view of the shortcomings of the existing technology, the purpose of the present invention is to provide a hydrogel material for quickly sealing retinal holes, its preparation method and application, which can quickly seal retinal holes in a weakly alkaline environment and has good tracing function, adhesion, injectability and biocompatibility. Compared with existing retinal sealing materials, its advantage is that it can quickly gel in the intraocular environment, avoiding the risks brought by material flow; the addition of fluorescein components can produce a fluorescent reaction under short-wavelength light, so that the material can produce a fluorescent reaction under short-wavelength light irradiation, providing a simple observation method for the material, which is convenient for intraoperative and postoperative observation. Since it has no obvious fluorescent reaction under natural light, the impact on the patient's visual effect can be minimized; and the material can seal retinal holes without performing a vitrectomy operation, which can reduce surgical trauma, is expected to accelerate postoperative recovery, improve postoperative quality of life and prevent the occurrence of postoperative complications.

[0009] The technical solution adopted in the present invention is as follows: In the first aspect of the present invention, a fluorescently traceable hydrogel material for sealing retinal breaks is provided. The hydrogel material is made of four-arm polyethylene glycol-maleimide 4-Arm-PEG-Mal, four-arm polyethylene glycol-thiol 4-Arm-PEG-SH, and fluorescein-maleimide FLS-5-Mal as raw materials, and is cross-linked through Michael addition reactions of maleimide (Mal) and thiol (SH) and maleimide (Mal) and fluorescein (FLS-Mal) to obtain a four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol / fluorescein complex, which is a fluorescently traceable hydrogel material for sealing retinal breaks.

[0010] In one or some embodiments of the present invention, the molecular weight of the 4-Arm-PEG-Mal is 5000 Da, and the molecular weight of the 4-Arm-PEG-SH is 5000 Da.

[0011] The hydrogel material of the present invention is a method for making a transparent material visible by cross-linking a fluorescein component and irradiating it with short-wavelength light to produce a fluorescent reaction.

[0012] In a second aspect of the present invention, a method for preparing a precursor solution of the fluorescently traceable hydrogel material for sealing retinal holes is provided, the method comprising the following steps: S1. A predetermined amount of four-arm polyethylene glycol-thiol and fluorescein-maleimide solid powders are thoroughly mixed and a predetermined amount of ultrapure water is added to fully dissolve the mixture, and the pH is adjusted to a weakly acidic state to obtain solution 1. S2. Add a set amount of four-arm polyethylene glycol-maleimide to a set amount of ultrapure water to fully dissolve it, and adjust the pH to weak acidity to obtain solution 2; S3. Mixing solution 1 and solution 2 according to a set ratio to obtain a hydrogel precursor solution.

[0013] When in use, the precursor solution of the hydrogel is added to the desired location of the retinal hole to form a fluorescently traceable hydrogel material for sealing the retinal hole.

[0014] In one or some embodiments of the present invention, in S1, the concentration of four-arm polyethylene glycol-thiol in solution 1 is 1% to 10% (w / w), and the molar ratio of four-arm polyethylene glycol-thiol to fluorescein-maleimide is 1:1. The present invention selects an appropriate fluorescein-maleimide ratio. Fluorescent material added via covalent crosslinking requires the fluorescein to react with the original components to form a molecular structure with fluorescent properties. This crosslinking is not a simple mixing process; it requires consideration of the reactive groups and environment of the fluorescein. The fluorescent property is bound to the molecular structure and requires an appropriate ratio to prevent fluorescein loss and release during the hydrogel's existence. Fluorescent material released into the vitreous environment could cause toxic reactions to the retina, leading to increased uncontrollability of the intraocular environment. Furthermore, this fluorescence requires short-wavelength light excitation, so it remains transparent under natural light. Short-wavelength light excitation is relatively easy to implement clinically. Therefore, the improvement brought to the material by crosslinking fluorescein is its safe and stable visual performance, enabling its application in retinal break sealing. The present invention uses cross-linked fluorescein-maleimide and no precipitation of fluorescein is found during use, thus maintaining stable fluorescence performance.

[0015] In one or some embodiments of the present invention, in S2, the concentration of the four-arm polyethylene glycol-maleimide solution in the second solution is 1% to 10% (w / w).

[0016] In one or some embodiments of the present invention, the weakly acidic environment in S1 and S2 is to prevent the mixed solution in S3 from reacting too quickly, and its acidic pH value is generally controlled within 4≤pH<7.

[0017] In one or some embodiments of the present invention, in S3, the mass ratio of the mixed solution 1 to the mixed solution 2 is 1:1.

[0018] In one or some embodiments of the present invention, the hydrogel precursor solution obtained in S3 must be used within 10 minutes.

[0019] In a third aspect of the present invention, there is provided use of the hydrogel material described in the first aspect in preparing a retinal break sealing material.

[0020] Furthermore, the hydrogel material can achieve responsive retinal break sealing function under different intraocular environments such as balanced salt solution, vitreous body, and liquefied vitreous body.

[0021] Furthermore, the hydrogel material can seal retinal holes without vitrectomy to treat rhegmatogenous retinal detachment.

[0022] Furthermore, sealing of retinal tears can be achieved by injecting a hydrogel precursor solution around the retinal tears without performing vitrectomy.

[0023] Compared with the related art known to the inventors, one of the technical solutions of the present invention has the following beneficial effects: (1) The advantages of the present invention are that the preparation process is simple, it is easy to prepare on a large scale and market it, and it can be prepared into two components for storage. When used, only equal amounts need to be mixed, and it is convenient to use during surgery. When used, it can be delivered by syringe through a conventional 25G scleral puncture port, which is easy to operate and has a low learning cost. Due to the addition of fluorescent components, the observability of the material is improved, which facilitates intraoperative and postoperative inspection and evaluation. At the same time, no fluorescent reaction that affects the patient's visual quality occurs under natural light environment. It is an ideal clinical hemostatic material with broad market prospects.

[0024] (2) The chemically cross-linked retinal hole sealant of the present invention, comprising four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol / fluorescein, has a good sealing effect, low biotoxicity, good biocompatibility, and is safe to use. It also meets the requirements for the treatment of rhegmatogenous retinal detachment. Since the hydrogel is responsive and can quickly form a retinal hole seal upon contact with the intraocular environment, it can be used without vitrectomy. This can reduce surgical trauma, shorten surgical time, improve postoperative quality of life, and reduce the occurrence of surgical complications, thus contributing to the development of accelerated recovery surgery for retinal detachment. At the same time, since vitrectomy is not required, it can be promoted in hospitals without vitrectomy equipment, thereby reducing the cost of treating rhegmatogenous retinal detachment. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The accompanying drawings, which constitute a part of the specification of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0026] Figure 1 : Schematic diagram of the preparation of retinal break sealing materials and their application in the treatment of RRD.

[0027] Figure 2 :The effect of retinal sealing material on gelation in different intraocular environments.

[0028] Figure 3 :The effects of retinal sealing materials under different lighting conditions.

[0029] Figure 4 :Effects of retinal sealing materials on sealing retinal breaks in pig eyes Figure 1 .

[0030] Figure 5 :Effects of retinal sealing materials on sealing retinal breaks in pig eyes Figure 2 .

[0031] Figure 6 : Fundus photography of the therapeutic effect of retinal sealing materials in a rabbit retinal detachment model.

[0032] Figure 7 :The therapeutic effect of retinal sealing materials in rabbit retinal detachment model. B-ultrasound images of the eyes.

[0033] Figure 8 : OCT images of the therapeutic effect of retinal sealing materials in a rabbit retinal detachment model.

[0034] Figure 9 : Pathological sections of rabbit retina using retinal sealing materials.

[0035] Figure 10 : Cytocompatibility diagram of the prepared retinal sealing materials.

[0036] Figure 11 : Clinical observation results of retinal sealing materials without added fluorescein. DETAILED DESCRIPTION

[0037] It should be noted that the following detailed descriptions are exemplary and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs.

[0038] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations and / or combinations thereof.

[0039] Against the backdrop of the increasing number of retinal detachment surgeries in China and the rapid rise of minimally invasive surgery and accelerated recovery after surgery concepts, the clinical demand for retinal hole sealing materials that can reduce surgical trauma, reduce the incidence of postoperative complications, and improve patient prognosis and quality of life has become particularly urgent. The present invention seals retinal holes by avoiding vitrectomy operations, thereby reducing surgical trauma. At the same time, it can treat rhegmatogenous retinal detachment in medical facilities without vitrectomy conditions. In the present invention, the material has fluorescent visualization characteristics by cross-linking fluorescein in a four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol structure, and can produce a fluorescent reaction under short-wavelength light irradiation, which provides a simpler visualization method for retinal sealing materials.

[0040] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0041] Example 1. Preparation of a chemically cross-linked retinal hole sealing material based on four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol / fluorescein Use an analytical balance to weigh 10 mg of 4-Arm-PEG-SH (molecular weight 5000 Da), 0.1 mg of FLS-5-Mal (specific chemical structure see schematic diagram) Figure 1 After thoroughly mixing the solids, dissolve them in 100 μL of double-distilled deionized water. Ultrasonication can be used to dissolve the solids to create a 10 w / w% solution. Weigh 10 mg of 4-Arm-PEG-Mal (molecular weight 5000 Da) and dissolve it in 100 μL of double-distilled deionized water to create a 10 w / w% solution. Combine the two solutions in a syringe and coat the outside of the syringe needle with medical silicone. Use the solution within 10 minutes.

[0042] Example 2: Application of a chemical cross-linked gel based on four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol / fluorescein in sealing retinal holes in isolated pig eye retinas Freshly excised porcine eyes (≤5 hours old) were used as experimental material. An 18mm corneal trephine was used to drill through the posterior pole of the eye, centered on the optic nerve, to obtain tissue from the sclera to the retina. The anterior segment structures (cornea, iris, lens, etc.) and vitreous humor were removed to create the posterior segment model required for the experiment.

[0043] 1. Such as Figure 2 As shown in Figure 2, when a balanced salt solution, vitreous humor, and liquefied vitreous humor were used to simulate the intraocular environment, the hydrogel precursor solution was injected smoothly from a 25 G needle onto the isolated retina, and the hydrogel precursor solution quickly gelled. The fluorescence effect of the hydrogel block under different light conditions is shown in Figure 2. Figure 3 shown.

[0044] 2. A retinal tear with a diameter of approximately 1 optic disc diameter (PD) was created in the retina of the eye cup. Two groups were set up for the experiment: ① The experimental group used 50μl of hydrogel to seal the retinal tear; ② The control group used 50μl of saline injected into the retinal tear. After the injection, both groups used saline to shock the retinal tear and observe whether the retina detached. Figure 4As shown, after hydrogel sealing, the retina remained attached to the scleral wall under the impact of saline flow. In the control group, the same amount of saline was used without hydrogel sealing, and the retina detached and floated under the flow of saline. This shows that the material has a good effect in sealing retinal holes.

[0045] 3. Make a puncture through the entire eyecup. Three groups were set up for the experiment: ① The experimental group used 50μl of hydrogel to seal the retinal tear at the puncture site; ② The control group injected 50μl of normal saline at the puncture site; ③ The untreated group did not puncture the eyecup. Subsequently, the eyecup was irrigated with sodium fluorescein solution. After inverting the eyecup, observe whether there is fluorescein leakage in the sclera. Figure 5 As shown in the figure, after the retina at the puncture site was sealed with hydrogel, no fluorescein leakage was observed outside the sclera wall; in contrast, after treatment with normal saline, fluorescein leakage was observed behind the sclera wall, indicating that the material had a good sealing effect on the retinal hole.

[0046] Example 3: Application of a chemical cross-linked gel based on four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol / fluorescein to seal retinal holes in a rabbit rhegmatogenous retinal detachment model The blue rabbits (SPF grade) used in the experiment were purchased from Shandong Ailek Biotechnology Co., Ltd. The animals were 10-12 weeks old and weighed 2.2-2.5 kg. All animals have passed the standardized production qualification review and quarantine process, and slit lamp and binocular microscope examinations were used to confirm that there were no pathological changes in the anterior chamber and posterior segment structures of the eyes. All experiments were performed only on the right eyes of the experimental animals. Before the operation, the animals were anesthetized by intramuscular injection of ketamine hydrochloride (20 mg / kg) and xylazine (5 mg / kg). Use iodine tincture disinfectant to disinfect the eyelid skin, 0.05% povidone eyewash to disinfect the ocular surface, spread a sterile drape and use a lid speculum to open the eyelid. Figure 1 As shown, a standard three-channel PPV was performed using a vitrectomy device connected to a 25G vitrectomy system, removing the central and peri-medullary vitreous. Using a microinjection needle, approximately 0.5 ml of BSS was injected subretinaally at a position approximately 2 PD below the optic disc, creating a retinal detachment approximately 4 PD in diameter. After the retinal detachment was created, the microinjection needle was swung to enlarge the retinal break to approximately 1 PD in diameter.

[0047] The experimental animals were divided into two groups. After the RRD animal model was established in the experimental group, 50 μl of hydrogel precursor solution was aspirated into the syringe. Under contact ophthalmoscope observation, a 25G injection needle was used to inject the hydrogel solution into the retinal tear through the vitrectomy channel. The control group was injected with 50 μl of normal saline at the retinal tear site. After injection, the injection needle was slowly withdrawn and the scleral puncture was sutured with 8-0 sutures. Within 7 days after surgery, 0.5% levofloxacin eye drops were used to prevent infection in the operated eyes 4 times a day. Clinical examinations including laser scanning fundus photography, ocular B-ultrasound and optical coherence tomography (OCT) were performed on the 1st, 7th, 14th and 21st days after surgery. All examinations were performed after ocular surface anesthesia with 0.4% oxybuprocaine hydrochloride eye drops. Before each fundus examination, 0.5% compound tropicamide eye drops were used to dilate the pupil. The therapeutic effects of rhegmatogenous retinal detachment are as follows: Figure 6 、 Figure 7 、 Figure 8 As shown, it can be observed that the range of retinal detachment in experimental animals whose retinal holes were sealed with the material gradually shrank and recovered, while the range of retinal detachment in the control group whose holes were not sealed gradually increased and proliferative membrane traction occurred.

[0048] After the observation, the eyeballs of the experimental animals using the retinal sealing material were subjected to pathological tissue observation, and the untreated normal rabbit eyes were used as controls for HE staining and Masson staining. The results are as follows: Figure 9 As shown in the figure, HE staining results showed that there was no significant difference in retinal tissue morphology between the hydrogel group and the control group. Masson staining results showed that no fibrous proliferative membrane was observed before the retina in the hydrogel group.

[0049] Example 4: Cytocompatibility determination of a chemical cross-linked gel based on four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol / fluorescein for sealing retinal holes in a rabbit rhegmatogenous retinal detachment model Specific steps of cell compatibility experiment: M / PI analysis RF / 6A and RPE cells (2×10 4Cells were seeded in 24-well plates. Each well containing RPE cells received 500 µL of DMEM-F12 medium supplemented with 10% (v / v) fetal bovine serum and 1% penicillin / streptomycin, while each well containing RF / 6A cells received 500 µL of MEM medium with the same supplements. All cells were cultured for one day at 37°C in a humidified atmosphere with 5% CO₂ to promote cell adhesion. Both cell types were randomly divided into two groups: ① a control group, which received fresh culture medium; and ② a hydrogel group, which received hydrogel-extraction culture medium. At 24, 48, and 72 hours, cells were stained using the AM / PI labeling kit (Solarbio, Beijing, China, CA1630-500T) according to the instructions. Fluorescence images recorded using an inverted fluorescence microscope were used to observe cell growth and viability in each group. In these images, live cells appear green, while dead cells appear red. CCK-8 analysis Cell Counting Kit-8 (CCK-8) was used to assess the cell viability of RF / 6A and RPE. Each well containing RPE cells received 500µL of DMEM-F12 medium supplemented with 10% (v / v) fetal bovine serum and 1% penicillin / streptomycin, while each well containing RF / 6A cells received 500µL of MEM medium containing the same supplements. All cells were cultured in a humidified environment at 37°C and 5% CO2 for one day to promote cell adhesion. The two cell types were then randomly divided into two groups: ① control group, fresh culture medium was replaced; ② hydrogel group, hydrogel extraction culture medium was replaced. At 24h, 48h and 72h of culture, the culture medium was discarded and fresh culture medium containing 10% CCK-8 was added. After incubation for 1 hour, the optical density (OD) value was measured at 450 nm using a microplate reader (SynergyH1 / H1M, Bio-Tek, China). The results are shown in Figure 2. Figure 10 As shown, the two methods observed no significant difference in cell activity between the hydrogel group cells and the control group cells, indicating good cell compatibility of the material.

[0050] Example 5: Observation of the effect of four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol chemical crosslinking gel without crosslinking fluorescein in a rabbit rhegmatogenous retinal detachment model The same model preparation method was used for the rabbits in the hydrogel group in Example 3. A fluorescein-free four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol mixed precursor solution was used to seal the retinal holes. Within 7 days after surgery, 0.5% levofloxacin eye drops were used to prevent infection in the operated eyes 4 times a day. Fundus photography and OCT observation were performed on the 7th day after surgery. Figure 11 As shown, it is difficult to observe the state of the hydrogel during examination, and it is also difficult to observe the amount and location of the injected hydrogel under an intraoperative microscope.

[0051] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be considered as equivalent replacement methods and are included in the scope of protection of the present invention.

Claims

1. A fluorescent traceable hydrogel material for sealing retinal holes, characterized in that: The hydrogel material uses four-arm polyethylene glycol-maleimide 4-Arm-PEG-Mal, four-arm polyethylene glycol-thiol 4-Arm-PEG-SH and fluorescein-maleimide FLS-5-Mal as raw materials, and is cross-linked through Michael addition reactions of maleimide (Mal) and thiol (SH) and maleimide (Mal) and fluorescein (FLS-Mal) to obtain a four-arm polyethylene glycol-maleimide / four-arm polyethylene glycol-thiol / fluorescein complex.

2. The fluorescent traceable hydrogel material for sealing retinal holes according to claim 1, wherein: The molecular weight of the 4-Arm-PEG-Mal is 5000 Da, and the molecular weight of the 4-Arm-PEG-SH is 5000 Da.

3. A method for preparing a precursor solution of a fluorescently traceable hydrogel material for sealing retinal breaks according to claim 1 or 2, characterized in that: The method comprises the following steps: S1. A predetermined amount of four-arm polyethylene glycol-thiol and fluorescein-maleimide solid powders are thoroughly mixed and a predetermined amount of ultrapure water is added to fully dissolve the mixture, and the pH is adjusted to a weakly acidic state to obtain solution 1. S2. Add a set amount of four-arm polyethylene glycol-maleimide to a set amount of ultrapure water and fully dissolve it, and adjust the pH to weak acidity to obtain solution 2; S3. Mixing solution 1 and solution 2 according to a set ratio to obtain a hydrogel precursor solution.

4. The method for preparing a precursor solution of a fluorescently traceable hydrogel material for sealing retinal holes according to claim 3, wherein: When in use, the precursor solution of the hydrogel is added to the desired location of the retinal hole to form a fluorescently traceable hydrogel material for sealing the retinal hole.

5. The method for preparing a precursor solution of a fluorescently traceable hydrogel material for sealing retinal holes according to claim 3, wherein: In S1, the concentration of four-arm polyethylene glycol-thiol in the solution 1 is 1% to 10% (w / w), and the molar ratio of the four-arm polyethylene glycol-thiol to fluorescein-maleimide is 1:

1.

6. The method for preparing a precursor solution of a fluorescently traceable hydrogel material for sealing retinal holes according to claim 3, wherein: In the S2, the concentration of four-arm polyethylene glycol-maleimide in the second solution is 1% to 10% (w / w).

7. The method for preparing a precursor solution of a fluorescently traceable hydrogel material for sealing retinal holes according to claim 3, wherein: In the above-mentioned S1 and S2, the weakly acidic pH is: 4≤pH<7.

8. The method for preparing a precursor solution of a fluorescently traceable hydrogel material for sealing retinal holes according to claim 3, wherein: In S3, the mass ratio of the mixed solution 1 to the mixed solution 2 is 1:

1.

9. Use of the hydrogel material according to claim 1 or 2 in preparing retinal break sealing materials.

10. The use according to claim 9, characterized in that: The hydrogel material can achieve a responsive retinal break sealing function in a balanced salt solution, vitreous, liquefied vitreous or other different intraocular environments; the hydrogel material can seal retinal breaks to treat rhegmatogenous retinal detachment without vitrectomy.

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