Contact lens loaded with amnion, preparation method therefor and use thereof

Abstract

Provided in the present invention are a contact lens loaded with an amnion, a preparation method therefor and the use thereof. The present invention provides an innovation for an adhesion method for the amnion and the contact lens, changes the previous method of simply adhering the amnion onto the contact lens by using a medical biological adhesive, simplifies an adhesion procedure for the amnion and the contact lens, and is suitable for industrial application. The present invention solves the problems of a reduced mechanical support force, amnion rupturing and uneven coverage of a conventional-suture-type amnion occurring as the conventional-suture-type amnion covers the ocular surface for an extended period of time. In terms of material optimization and selection, the present invention meets the basic requirement that an adhesive is non-toxic and harmless, and also takes into consideration biocompatibility requirements and the requirements of the cornea for the oxygen permeability of the contact lens. The use of the amnion is more comfortable, complex surgical procedures are not required, and irritation caused by sutures is also avoided. A design solution in which the contact lens serves as an amnion support enables an amniotic lens to better support and protect a covered ocular surface.

Description

Amniotic membrane loaded contact lens and preparation method and application thereof TECHNICAL FIELD

[0001] The present application relates to the field of biomedical materials, in particular, to an amniotic membrane loaded contact lens and preparation method and application thereof. BACKGROUND

[0002] Corneal epithelial defect is a common clinical problem in ophthalmology, which is often caused by various non-infectious factors such as mechanical trauma, chemical burns, dry eye, neurotrophic keratitis, autoimmune diseases, etc. If the corneal epithelial defect cannot be effectively repaired for a long time, it may cause a series of serious complications, including corneal ulcer and corneal perforation, which not only seriously affects the vision, but also may even lead to blindness.

[0003] Amniotic membrane is the inner layer of placenta, which has unique biological properties and is widely used in the field of ophthalmology. Its main advantages include: anti-inflammatory properties: amniotic membrane contains various anti-inflammatory factors, which can reduce inflammatory response and help the treatment of ocular surface diseases; anti-scarring: the matrix components in amniotic membrane can inhibit the activity of fibroblasts and prevent scarring; promote healing: amniotic membrane is rich in growth factors, which can promote cell proliferation and migration and accelerate wound healing; antibacterial properties: amniotic membrane has certain antibacterial activity, which can reduce the risk of infection.

[0004] Due to these advantages, amniotic membrane is used in various ophthalmic surgeries and treatments. Traditional amniotic membrane transplantation is performed under topical anesthesia or peribulbar block anesthesia by suturing the amniotic membrane to the corneal surface, however, the suture fixation method has the disadvantages of complex operation, long operation time, suture foreign body stimulation, etc. The suturing process may also increase the risk of infection and may cause additional mechanical damage to the patient's cornea. In addition, if the sutured amniotic membrane is damaged, it may break down prematurely and may require a second surgery, increasing the patient's pain and economic burden. SUMMARY

[0005] The present application solves the problem of inconvenient application and poor comfort of existing amniotic membrane by preparing amniotic membrane powder into a pre-polymer solution and combining it with a treated contact lens to prepare a wearable amniotic membrane contact lens, which improves the treatment effect and improves the wearing experience of patients, providing an effective solution for ophthalmic clinical treatment.

[0006] In a first aspect of the present application, a preparation method of an amniotic membrane loaded contact lens is provided, comprising:

[0007] Preparation of amniotic membrane reconstituted pre-polymer solution: uniformly mix methacrylated gelatin, lithium phenyl-2,4,6-trimethylbenzoyl phosphinate and amniotic membrane powder to obtain a mixed solution; after sterilization treatment of the mixed solution, an amniotic membrane reconstituted pre-polymer solution is obtained;

[0008] Preparation of contact lens treating solution: mixing the methacrylated gelatin and the lithium phenyl-2,4,6-trimethylbenzoylphosphinate uniformly to obtain the contact lens treating solution;

[0009] Pre-treatment of the contact lens: immersing the contact lens in the contact lens treating solution to obtain the pre-treated contact lens;

[0010] Coating the amniotic membrane recombination pre-polymer solution on the surface of the pre-treated contact lens; and irradiating to cause in-situ solidification and cross-linking to obtain the contact lens loaded with the amniotic membrane.

[0011] The present application does not limit the preparation and sterilization of the amniotic membrane recombination pre-polymer solution, the preparation of the contact lens treating solution, and the operation sequence of the pre-treatment of the contact lens in the above steps. The preparation and sterilization of the amniotic membrane recombination pre-polymer solution, the preparation of the contact lens treating solution, and the pre-treatment of the contact lens can be completed before the coating of the amniotic membrane recombination pre-polymer solution on the surface of the pre-treated contact lens.

[0012] Preferably, the pore diameter of the methacrylated gelatin after photocuring is between 10 um and 200 um, and the porosity is 30-60%.

[0013] More preferably, the pore diameter of the methacrylated gelatin after photocuring is between 100 um and 200 um, and the porosity is 50-60%.

[0014] Preferably, the contact lens is a soft hydrophilic contact lens, and the water content is 34-40%.

[0015] Preferably, the mass percentage concentration of the methacrylated gelatin, the lithium phenyl-2,4,6-trimethylbenzoylphosphinate, and the amniotic membrane powder in the amniotic membrane recombination pre-polymer solution is 6-8%, 0.2-0.5%, and 20-50%, respectively.

[0016] Preferably, the mass percentage concentration of the methacrylated gelatin and the lithium phenyl-2,4,6-trimethylbenzoylphosphinate in the contact lens treating solution is 6-8% and 0.2-0.5%, respectively.

[0017] Preferably, the contact lens is completely immersed in the contact lens treating solution at 15-40℃ for 20-60 minutes.

[0018] Preferably, the irradiation condition is that the wavelength is between 320 and 400 nm, and the irradiation time is 30-120 seconds.

[0019] In the second aspect of the present application, the contact lens loaded with the amniotic membrane prepared by the preparation method of the contact lens loaded with the amniotic membrane is provided.

[0020] In the third aspect of the present application, the preparation method of the contact lens loaded with the amniotic membrane and the application of the contact lens loaded with the amniotic membrane in the preparation of a medical device for treating or alleviating corneal epithelial defects and promoting the repair of corneal epithelial cells are provided.

[0021] In a fourth aspect of the present application, a kit for preparing the amniotic membrane-loaded contact lens is provided, comprising the amniotic membrane recombination pre-polymer solution and the contact lens treatment solution.

[0022] The wearable amniotic membrane-loaded contact lens of the present application has the following beneficial effects:

[0023] 1. The adhesion method of the amniotic membrane and the contact lens is innovative, which changes the previous simple adhesion of the amniotic membrane and the contact lens by medical biological glue, simplifies the adhesion procedure of the amniotic membrane and the contact lens, and is suitable for industrial application.

[0024] 2. The problem of the decrease of mechanical support force, the rupture of the amniotic membrane and the uneven coverage caused by the increase of the time of covering the ocular surface of the traditional suture type amniotic membrane is solved.

[0025] 3. The optimization and selection of the material of the present application not only meet the basic requirement of non-toxic and harmless of the adhesive, but also take into account the biocompatibility and the oxygen permeability requirement of the contact lens to the cornea.

[0026] 4. The use of the amniotic membrane is more comfortable, without complex surgical procedures and irritation caused by sutures.

[0027] 5. The design scheme of the contact lens as the support of the amniotic membrane makes the amniotic membrane lens can provide better support and protection for the covered ocular surface. BRIEF DESCRIPTION OF DRAWINGS

[0028] Fig. 1 is a photograph of a wearable amniotic membrane contact lens.

[0029] Fig. 2 is a general photograph of the cornea of a rabbit before and after wearing the amniotic membrane contact lens in Comparative Example 1.

[0030] Fig. 3 is a fluorescein sodium staining diagram of the cornea in Comparative Example 1.

[0031] Fig. 4 is the healing rate of the cornea in Comparative Example 1.

[0032] Fig. 5 is a photograph of the corneal slit lamp and a fluorescein sodium staining diagram of the cornea of the PEGDA group in Comparative Example 2.

[0033] Fig. 6 is a photograph of the corneal slit lamp and a fluorescein sodium staining diagram of the cornea of the ordinary GelMA group in Comparative Example 2. DETAILED DESCRIPTION

[0034] In order to solve the technical problems of single amniotic membrane transplantation method, complex operation, low patient comfort and limited protection performance, the present application provides a wearable amniotic membrane-loaded contact lens and a preparation method and application thereof. The purpose of the present application is achieved by the following technical scheme.

[0035] The preparation method of the wearable amniotic membrane contact lens (amniotic membrane contact lens) comprises the following steps:

[0036] S1. Preparing an amniotic membrane recombination pre-polymer solution: uniformly mixing methacrylated gelatin (GelMA hydrogel), lithium phenyl-2,4,6-trimethylbenzoyl phosphinate (LAP) and amniotic membrane powder to obtain a mixed solution;

[0037] Preferably, the mass percentage concentrations of the GelMA hydrogel, the lithium phenyl-2,4,6-trimethylbenzoyl phosphinate (LAP) and the amniotic membrane powder in the mixed solution are 6-8%, 0.2-0.5% and 20-50% respectively; more preferably, the mass percentage concentrations are 6-8%, 0.2-0.5% and 20-30% respectively.

[0038] Preferably, the pore diameter of the GelMA hydrogel after photocuring is between 10um and 200um, and the porosity is 30-60%.

[0039] More preferably, the pore diameter of the GelMA hydrogel after photocuring is between 100um and 200um, and the porosity is 50-60%.

[0040] In the present application, the solvent used for dissolving the GelMA hydrogel, the LAP and the amniotic membrane powder is not limited, and can be water, distilled water or deionized water.

[0041] The present application does not limit the uniform mixing method, which can be completed by the skilled person in the art according to the conventional operation.

[0042] S2. After sterilizing the mixed solution, an amniotic membrane recombination pre-polymer solution is obtained.

[0043] The present application does not limit the sterilization method, which can be completed by the skilled person in the art according to the conventional operation. Preferably, the pasteurization is adopted.

[0044] S3. Preparing a contact lens treatment solution: uniformly mixing the GelMA hydrogel and the LAP to obtain a contact lens treatment solution.

[0045] Preferably, the mass percentage concentrations of the GelMA hydrogel and the LAP in the treatment solution are 6-8% and 0.2-0.5% respectively.

[0046] In the present application, the solvent used for dissolving the GelMA hydrogel and the LAP is not limited, and can be water, distilled water, deionized water or PBS phosphate buffer.

[0047] The present application does not limit the uniform mixing method, which can be completed by the skilled person in the art according to the conventional operation.

[0048] S4. Pre-treating the contact lens: immersing the contact lens in the contact lens treatment solution to obtain a pre-treated contact lens.

[0049] The present application does not limit the way of soaking, and the skilled in the art can complete it according to the conventional operation. Alternatively, the contact lens is completely soaked in the contact lens treating solution for 20-60 minutes at 15-40℃.

[0050] The present application does not limit the order of preparation of the amniotic membrane recombination pre-polymer solution and the contact lens treating solution. The amniotic membrane recombination pre-polymer solution can be prepared first, and then the contact lens treating solution; or the contact lens treating solution can be prepared first, and then the amniotic membrane recombination pre-polymer solution; or the amniotic membrane recombination pre-polymer solution and the contact lens treating solution can be prepared simultaneously.

[0051] The step of pretreating the contact lens can be performed immediately after the preparation of the contact lens treating solution is completed, or can be performed at another time according to actual needs.

[0052] S5. The amniotic membrane recombination pre-polymer solution obtained in step S2 is uniformly coated on the surface of the pretreated contact lens in step S4; and light is irradiated to cause in-situ curing and crosslinking to obtain a wearable amniotic membrane contact lens.

[0053] The present application does not limit the amount of the amniotic membrane recombination pre-polymer solution to be coated, and the skilled in the art can coat different amounts of the amniotic membrane recombination pre-polymer solution on the surface (for example, the inner surface optical zone, the entire inner surface, or the entire inner and outer surface) of the pretreated contact lens according to actual needs.

[0054] Preferably, the amniotic membrane recombination pre-polymer solution is coated on the inner surface of the pretreated contact lens.

[0055] The loading amount of the amniotic membrane can be adjusted by the concentration and the coating amount of the amniotic membrane recombination pre-polymer solution. For example, 90ul of the amniotic membrane recombination pre-polymer solution containing 20%-30% amniotic membrane powder is coated on the inner surface of the contact lens for curing and crosslinking, and the loading amount of the amniotic membrane per contact lens is 23mg / lens.

[0056] In the present application, the inner surface optical zone of the contact lens refers to the central part of the optical area of the back surface of the contact lens, and the radius of curvature of this part is designed to match the shape of the cornea to ensure that the light passing through this area can be clearly focused on the retina.

[0057] Preferably, the contact lens is a soft hydrophilic contact lens with a water content of 34-40%. When the water content is greater than 40%, it is not conducive to the adhesion of the amniotic membrane recombination pre-polymer solution.

[0058] Preferably, the light irradiation conditions are: wavelength between 320 and 400 nanometers, and irradiation time of 30-120 seconds.

[0059] The method further comprises a pretreatment step of the amniotic membrane, which comprises: taking fresh amniotic membrane, washing with sterile normal saline, and then placing in antibiotic normal saline for rinsing; scraping off the sponge layer, part of the fibroblast layer and serous exudate under a microscope; attaching a sterile nitrocellulose membrane (N.C membrane) to the amniotic membrane, with the epithelial surface of the amniotic membrane facing upward; and trimming to a suitable size according to actual needs.

[0060] The method further comprises a preparation step of the amniotic membrane powder, which comprises: pre-freezing the amniotic membrane treated with sterilization, for example, placing in a-80 DEG C refrigerator for 20 min; freeze-drying the pre-frozen amniotic membrane, for example, using a vacuum freeze dryer at-53 DEG C for 48 h; and grinding the freeze-dried amniotic membrane into powder, for example, transferring the amniotic membrane cut into small pieces to a centrifuge tube containing grinding beads, using a grinder at 30 times / s, 90 s, 3 times, and grinding into powder.

[0061] The method further comprises a post-treatment step, that is, washing the amniotic membrane after reaction, pre-treating the contact lens, and the amniotic membrane contact lens: placing them in a buffer solution for washing, to remove unreacted reagents and by-products.

[0062] In the present application, the buffer solution used for washing the reaction has no limitation, and a person skilled in the art can select it according to the actual situation, for example, PBS buffer solution.

[0063] In the present application, the number of washing times and the time have no limitation, and a person skilled in the art can determine them according to the actual situation, for example, 3-10 times of washing, 2-60 minutes each time.

[0064] The technical scheme of the present application is based on the following principle: GelMA (gelatin methacrylate) is a photosensitive biomaterial synthesized by reacting the amine group (-NH2) on the gelatin molecule with methacrylic anhydride (MA) to introduce a methacrylate group (-C(=O)OCH3). This modification endows gelatin with the ability of photocrosslinking, that is, under the irradiation of ultraviolet light, GelMA can quickly form a stable three-dimensional network structure. Porous GelMA hydrogel is a material with a special microstructure, and its porous structure can provide more space and more efficient material exchange channels, which is beneficial to the proliferation, growth of cells and the transmission of nutrients and metabolic waste.

[0065] Preparation of porous GelMA hydrogel generally involves mixing GelMA with another polymer to form a biphasic or multiphasic system. For example, by mixing GelMA with polyethylene glycol (PEO), hydrogels with different porosities can be created. By adjusting the volume fraction of PEO and mixing time, the size of the pore diameter and porosity can be controlled. In the present invention, the GelMA hydrogel is a porous GelMA hydrogel with a pore diameter of 10-200 um and a porosity of 30-60%, so that the amniotic membrane contact lens has good oxygen permeability and can be worn for a long time without causing corneal hypoxia.

[0066] The present invention is further illustrated by the following examples which are intended to be illustrative only and should not be considered limiting in scope. Unless otherwise defined, the technical and scientific terms used herein have the meanings that are commonly understood by one of ordinary skill in the art to which this invention belongs. Where a specific condition is not indicated in the examples, the conventional conditions or the conditions recommended by the manufacturer are followed. Where the manufacturer of the reagent or instrument is not indicated, it is a conventional product that can be obtained commercially.

[0067] Material Sources

[0068] Amniotic membrane was obtained from the obstetrics of the provincial hospital or purchased from Guangzhou Ruatai Biological Technology Co., Ltd. (Biological amniotic membrane for ophthalmology, national medical device approval 20193161006); Jiangxi Ruizhi Biological Engineering Technology Co., Ltd. (Biological amniotic membrane, national medical device approval 20173160958).

[0069] High-porosity GelMA hydrogel was purchased from Suzhou Yongqinquan Intelligent Equipment Co., Ltd. The product model was EFL-GM-PR-001, with a porosity / pore diameter of 30-40% / 10-100 um; EFL-GM-PR-002, with a porosity / pore diameter of 50-60% / 100-200 um.

[0070] Contact lenses were purchased from Bausch & Lomb Co., Ltd. The product was a soft hydrophilic contact lens, with a water content of 36%, an oxygen permeability coefficient nominal value of 68.3 x 10 -11 (cm 2 / s) [mLO2 / (mL x hPa)], a lens diameter of 14 mm, a base curve radius of 8.6 mm, and a center thickness of 0.07 mm.

[0071] Example 1

[0072] The wearable amniotic membrane contact lens was prepared according to the following steps:

[0073] S1. Preparation of amniotic membrane recombination prepolymer solution: uniformly mix high porosity GelMA hydrogel (porous GelMA), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) and amniotic membrane powder to obtain a mixed solution.

[0074] To fully dissolve and mix the substances, the mixed solution can be placed in a 37°C constant temperature water bath for 15 min, shaken for 30 s after taking it out, and fully mixed. The above steps can be repeated according to actual needs, for example, three times.

[0075] S2. Pasteurize the mixed solution to obtain an amniotic membrane recombination prepolymer solution.

[0076] The mass percentage concentrations of high porosity GelMA hydrogel (porous GelMA), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) and amniotic membrane powder in the amniotic membrane recombination prepolymer solution are 6-8%, 0.2-0.5% and 20-50%, for example, 7%, 0.3%, 25%; 7.5%, 0.4%, 30%; 6%, 0.2%, 20%; 8%, 0.5%, 50%. The solvent is water.

[0077] The sterilization method is: 80°C constant temperature water bath, 30 min; 0°C ice water, 5 min; the above steps are repeated 3-5 times.

[0078] S3. Preparation of contact lens treatment solution: uniformly mix high porosity GelMA hydrogel (porous GelMA) and LAP to obtain a contact lens treatment solution.

[0079] The mass percentage concentrations of high porosity GelMA hydrogel (porous GelMA) and LAP in the treatment solution are 6-8% and 0.2-0.5%, for example, 6%, 0.2%; 7%, 0.4%. The solvent is PBS phosphate buffer.

[0080] S4. Pretreatment of the contact lens: immerse the contact lens in the contact lens treatment solution at room temperature (15-25°C) for 30 min to obtain a pretreated contact lens.

[0081] S5. Uniformly coat 80-100 ul, 20-30 ul of the amniotic membrane recombination prepolymer solution obtained in step S2 on the inner surface (the side facing or contacting the ocular surface) of the pretreated contact lens in step S4, and irradiate it under a UV lamp for 30 seconds to cause in-situ curing and crosslinking, thereby obtaining a wearable amniotic membrane-loaded contact lens (Figure 1).

[0082] To uniformly coat the amniotic membrane recombination prepolymer solution on the inner surface of the pretreated contact lens, place the contact lens coated with the amniotic membrane recombination prepolymer solution on an inner surface shaping mold, and then irradiate it under a UV lamp to complete the in-situ curing and crosslinking. After demolding, a wearable amniotic membrane contact lens is obtained.

[0083] Comparative Example 1

[0084] Twelve New Zealand white rabbits were used. After anesthesia, the epithelium was removed by a scalpel to remove the epithelium and basement membrane of the cornea within an 11 mm range. Six rabbits were randomly selected to wear the wearable amniotic contact lens prepared in Example 1 after the operation (amniotic lens group); the remaining 6 rabbits were not treated after the operation (control group). One day and two days after the operation, the corneal slit lamp was photographed and the fluorescein sodium staining was photographed, and the healing of various corneal epithelium and eye redness, secretion and other abnormalities were recorded. As shown in Figure 2, the schematic diagram of the experimental animals before and after wearing the amniotic lens, the contact lens fits well, and the transparency is good. As shown in Figure 3, the experimental group showed more natural blinking behavior, a small amount of sticky secretion, and a lighter inflammatory reaction because of the protection of the wearable amniotic contact lens 24 hours after the operation; the control group closed their eyes tightly because of epithelial damage, and the inflammatory reaction was obvious, and the conjunctival hyperemia was severe.

[0085] One month after the operation, the healing rate of the corneal epithelium of the two groups was calculated using Image J software (Figure 4), and the results showed that the healing rate of the amniotic lens group was significantly faster than that of the blank control group, and the difference was statistically significant.

[0086] Comparative Example 2

[0087] Grouping: Twelve New Zealand white rabbits were randomly divided into three groups, four in each group, namely the porous GelMA group, the PEGDA group, and the ordinary GelMA group.

[0088] The rabbits were anesthetized and the epithelium was removed by a scalpel to remove the epithelium and basement membrane of the cornea within an 11 mm range.

[0089] In the porous GelMA group, the wearable amniotic contact lens prepared in Example 1 was worn after the operation.

[0090] In the PEGDA group, the PEGDA-based amniotic lens was worn after the operation.

[0091] The difference between the PEGDA-based amniotic lens and the amniotic contact lens prepared in Example 1 is that the former is not loaded with a pretreated corneal contact lens. The oxygen permeability of PEGDA is poor after photocuring, and the loading of an additional layer of corneal contact lens will further reduce the oxygen permeability. In addition, due to the material properties of 0.2% PEGDA, it has poor ductility and high brittleness, and cannot be well adapted to the contact lens. The specific preparation steps are as follows:

[0092] Steps S1 and S2 are the same as in Example 1.

[0093] S3. 20-30ul, for example 25ul, of the amniotic PEGDA mixture was added to the contact lens molding mold, the mold was uniformly pressed, the amniotic PEGDA mixture was molded, and then in-situ curing and crosslinking were completed under ultraviolet light. After demolding, the PEGDA-based amniotic contact lens was obtained.

[0094] The ordinary GelMA group is given a normal GelMA-based amniotic membrane lens after surgery.

[0095] The preparation method of the ordinary GelMA-based amniotic membrane lens is different from that in Example 1 in that it is not loaded with a pretreated contact lens. The preparation steps of the ordinary GelMA-based amniotic contact lens are as follows:

[0096] Steps S1 and S2 are the same as in Example 1.

[0097] S3. 20-30ul, for example 25ul, of the amniotic GelMA mixed solution is added to the contact lens molding mold, the mold is uniformly pressed, the amniotic GelMA mixed solution is molded, and then in-situ solidification and crosslinking are completed under ultraviolet light. After demolding, the GelMA-based amniotic contact lens is obtained.

[0098] Corneal slit lamp photography and fluorescein sodium staining photography are performed at 1 day, 3 days, and 5 days after surgery (Figures 5 and 6), and various corneal epithelial healing conditions and eye redness, secretions, and other abnormal conditions are recorded.

[0099] The results show that:

[0100] The porous GelMA group: In the 36h postoperative observation, no lens shedding occurred. And the porous GelMA group showed a lighter inflammatory reaction, no conjunctival hyperemia, no ciliary hyperemia, faster healing effect, less secretion, and most importantly, no neovascularization.

[0101] The PEGDA group, due to its greater brittleness, in the postoperative follow-up observation, many lenses were shed due to lens brittle fracture. In the 12h postoperative observation, the lens shedding rate reached 50%, in the 24h postoperative observation, the lens shedding rate increased to 62%, in the 36h postoperative observation, the lens shedding rate reached 75%, and the proportion of lens shedding due to lens fragmentation reached 83%, that is, 5 of the 6 shed lenses were due to the brittleness of PEGDA.

[0102] Compared with the PEGDA group, the ductility of the ordinary GelMA lens is better, and lens shedding due to lens fragmentation rarely occurs. The main reason for lens shedding is that the material shrinks to a certain extent after solidification, causing the lens periphery to produce a certain amount of warping, affecting the close fitting of the lens with the ocular surface, and at the same time, its better biocompatibility and amniotic membrane release rate cause its degradation rate to be faster than that of the PEGDA-based amniotic contact lens, which also accelerates lens shedding. In the 12h postoperative observation, the lens shedding rate reached 37%, in the 24h postoperative observation, the lens shedding rate increased to 50%, in the 36h postoperative observation, the lens shedding rate reached 62%, and the proportion of lens shedding due to warping reached 40%, that is, 2 of the 5 shed lenses were due to warping, and the remaining 3 were degraded and shed as the observation time increased.

[0103] The PEGDA group and the common GelMA group showed more severe inflammatory reaction, more serious conjunctival congestion, more secretion, and more obvious photophobia behavior of rabbit eyes, and the eyes were tightly closed.

[0104] The above specific embodiments do not constitute a limitation on the protection scope of the present application. Those skilled in the art should understand that various modifications, combinations, sub-combinations, and substitutions can be made according to design requirements and other factors. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for preparing an amniotic membrane-loaded contact lens, comprising: preparing an amniotic membrane reconstituted pre-polymer solution by mixing methacrylated gelatin, lithium phenyl-2,4,6-trimethylbenzoylphosphinate and amniotic membrane powder to obtain a mixed solution, and then sterilizing the mixed solution to obtain the amniotic membrane reconstituted pre-polymer solution; preparing a contact lens treatment solution by mixing methacrylated gelatin and lithium phenyl-2,4,6-trimethylbenzoylphosphinate to obtain the contact lens treatment solution; pre-treating a contact lens by immersing the contact lens in the contact lens treatment solution to obtain a pre-treated contact lens; applying the amniotic membrane reconstituted pre-polymer solution to the surface of the pre-treated contact lens, and irradiating to cause in-situ solidification and cross-linking to obtain the amniotic membrane-loaded contact lens.

2. The method of claim 1, wherein the lens is a contact lens. The pore diameter of the methacrylated gelatin after photo-curing is between 10 um and 200 um, and the porosity is between 30% and 60%.

3. The method of claim 2, wherein the lens is a contact lens. The pore diameter of the methacrylated gelatin after photo-curing is between 100 um and 200 um, and the porosity is between 50% and 60%.

4. The method of claim 1, wherein the lens is a contact lens. The contact lens is a soft hydrophilic contact lens, and the water content is between 34% and 40%.

5. The method of claim 1, wherein the lens is a contact lens. The mass percentage concentrations of the methacrylated gelatin, lithium phenyl-2,4,6-trimethylbenzoylphosphinate and amniotic membrane powder in the amniotic membrane reconstituted pre-polymer solution are 6-8%, 0.2-0.5% and 20-50%, respectively.

6. The method of claim 5, wherein the lens is a contact lens. The mass percentage concentrations of the methacrylated gelatin, lithium phenyl-2,4,6-trimethylbenzoylphosphinate and amniotic membrane powder in the amniotic membrane reconstituted pre-polymer solution are 6-8%, 0.2-0.5% and 20-30%, respectively.

7. The method of claim 5, wherein the lens is a contact lens. The mass percentage concentrations of the methacrylated gelatin, lithium phenyl-2,4,6-trimethylbenzoylphosphinate and amniotic membrane powder in the amniotic membrane reconstituted pre-polymer solution are 7%, 0.3% and 25%, or 7.5%, 0.4% and 30%, or 6%, 0.2% and 20%, or 8%, 0.5% and 50%, respectively.

8. The method of claim 1, wherein the lens is a contact lens. The mass percentage concentrations of the methacrylated gelatin and lithium phenyl-2,4,6-trimethylbenzoylphosphinate in the contact lens treatment solution are 6-8% and 0.2-0.5%, respectively.

9. The method of claim 8, wherein the lens is a contact lens. The mass percentage concentrations of the methacrylated gelatin and lithium phenyl-2,4,6-trimethylbenzoylphosphinate in the contact lens treatment solution are 6%, 0.2%, or 7%, 0.4%, respectively, and the solvent is PBS phosphate buffer.

10. The method of claim 1, wherein the lens is a contact lens. The contact lens is completely immersed in the contact lens treatment solution for 20-60 minutes at 15-40℃.

11. The method of claim 10, wherein the lens is a contact lens. The contact lens is completely immersed in the contact lens treatment solution for 30 minutes at 15-25℃.

12. The method of claim 1, wherein the lens is a contact lens. The irradiation condition is: wavelength of 320-400 nm, and irradiation time of 30-120 seconds. 13.An amniotic membrane-loaded contact lens prepared by the method according to any one of claims 1-12. 14.Use of the method for preparing an amniotic membrane-loaded contact lens according to any one of claims 1-12 and the amniotic membrane-loaded contact lens according to claim 13 in the preparation of a medical device for treating or alleviating corneal epithelial defects and promoting the repair of corneal epithelial cells. 15.A kit for preparing an amniotic membrane-loaded contact lens, comprising the amniotic membrane reconstituted pre-polymer solution and the contact lens treatment solution according to any one of claims 1-12.

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