Frameless amniotic membrane mirror device, manufacturing method and using method

Abstract

The invention relates to the technical field of medical instruments, in particular to a frameless amniotic membrane mirror device, a manufacturing method and a using method, and the frameless amniotic membrane mirror device comprises an amniotic membrane tissue layer and a biocompatible thin film layer formed by spraying a mixed solution of polymethyl acrylate and polyvinyl alcohol; the overall diameter of the device is 14 mm, the rise of the device is 6.2 + / -0.1 mm, and the device can be directly implanted into the ocular surface to cover the cornea without a frame support. The manufacturing method comprises the steps of amniotic membrane treatment, model eye forming, mixed solution preparation, membrane spraying and forming, trimming and sterilization. The application method relates to implantation after surface anesthesia, fitting observation and subsequent taking-out. Through the frameless conformal fitting design, the problems that an existing framed amniotic membrane mirror is displaced and cannot be worn by a patient with strong foreign body sensation and shallow conjunctival sac are solved, and meanwhile secondary trauma of a suture operation is avoided. And the residual film after the amniotic membrane is dissolved can continuously provide protection, and the amniotic membrane has the advantages of good fitness, high patient comfort, simplicity and convenience in operation and good safety.

Description

Technical Field

[0001] This invention relates to the field of ophthalmic medical device technology, specifically to a frameless amniotic lens device, its manufacturing method, and its usage method. Background Technology

[0002] Corneal injury is a common ophthalmic disease, and amniotic membrane transplantation is an effective means to promote corneal epithelial repair and prevent scarring. Currently, the main forms of amniotic membrane used in clinical practice include: self-prepared fresh amniotic membrane, single biological amniotic membrane (dry / wet), and biological amniotic membrane with a frame support device (such as PROKERA in the United States).

[0003] However, existing technologies have obvious drawbacks: First, bringing your own fresh amniotic membrane presents challenges such as limited availability, risk of cross-infection, and legal and ethical issues. Second, a single piece of biological amniotic membrane needs to be sutured and fixed, which leads to secondary surgical trauma, strong foreign body sensation and inflammatory reaction in patients, and shortens the time the amniotic membrane is in place. Third, while the biological amniotic membrane with a frame support device (sutureless) simplifies the surgery, its rigid frame may cause the device to shift or have poor tracking ability. It is not suitable for patients with shallow conjunctival sacs and there is a risk of foreign body sensation and corneal scratching during removal.

[0004] Therefore, there is an urgent need in the field for an ocular surface repair device that can preserve the biological activity of the amniotic membrane while avoiding the drawbacks of sutures and borders. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a frameless amniotic membrane lens device, its manufacturing method, and its usage method. This device requires no sutures, has no rigid frame, can fit closely to the ocular surface, and can still provide continuous protection after the amniotic membrane dissolves, thereby improving patient comfort, simplifying clinical operations, and enhancing treatment outcomes.

[0006] This invention is achieved through the following technical solution: A frameless amnioscope device includes: an amniotic tissue layer and a thin film layer; The amniotic membrane tissue layer is formed and covers the surface of the model eye; A thin film layer formed by a mixed solution of polymethyl acrylate and polyvinyl alcohol is sprayed onto the surface of the amniotic membrane tissue layer. This amniotic membrane lens device requires no frame support and can be directly implanted into the conjunctival sac to cover the cornea. Furthermore, the biocompatible thin film layer remaining after the amniotic membrane dissolves still provides protection.

[0007] Preferably, the overall diameter of the device is 14 mm and the sagittal height is 6.2 ± 0.1 mm; the amniotic membrane tissue layer is a fresh amniotic membrane or a bioengineered amniotic membrane processed within 6 hours of ex vivo.

[0008] A method for manufacturing a frameless amniotic endoscope device includes the following steps: Step 1: Obtain fresh amniotic membrane tissue and perform chorionic villi removal and aseptic cleaning within 6 hours of extraction at 4°C. Step 2: Cover the surface of the model eye with the processed amniotic membrane tissue; Step 3: Prepare a mixed solution containing polymethyl acrylate and polyvinyl alcohol. Step 4: Spray the mixed solution onto the surface of the amniotic membrane tissue to form a composite layer with tension; Step 5: Trim the periphery of the amniotic membrane tissue to form a circular frameless amnioscope with a diameter of 14mm and a sagittal height of 6.2±0.1mm; Step 6: The obtained amnioscope is stored in a preservation solution at -20°C and sterilized by cobalt-60 radiation.

[0009] A further preferred method for preparing the mixed solution includes: adding low molecular weight polymethyl acrylate at 30% by weight to physiological saline to form an emulsion, dissolving polyvinyl alcohol at 4% by weight in physiological saline, and then mixing the two solutions to make the final concentration of polymethyl acrylate in the mixed solution 1% by weight.

[0010] A method of using a rimless amniotic endoscope device includes the following steps: Step 1: Administer topical anesthesia to the patient's ocular surface; Step 2: Use an eyelid speculum to open the eyelids and rinse the surface of the amniotic lens with sterile saline. Step 3: Use ophthalmic forceps to grasp the edge of the amniotic lens and implant it into the conjunctival sac to cover the cornea; Step 4: Gently close your eyes and rotate your eyeballs to make the amniotic lens fit against the surface of your eye; Step 5: Observe the bonding condition using a slit lamp; Step Six: After the corneal epithelium has repaired or the amniotic membrane has dissolved, remove the remaining membrane directly.

[0011] Further preferred, topical anesthesia is achieved using oxybuprocaine hydrochloride eye drops.

[0012] A further preferred approach is to remove the amniotic lens after complete corneal epithelial repair or after the amniotic membrane has dissolved.

[0013] This invention abandons the approach of adding external frames or mechanical anchoring, and instead adopts a more advanced biomimetic integration strategy. Its core principle is as follows: Structural biomimicry: The amniotic membrane is shaped directly using the curved surface of the model eye, so that the final shape of the amniotic lens (14mm in diameter, 6.2mm in sagittal height) closely matches the natural shape of the anterior surface of the human cornea. This allows it to adhere to the ocular surface like a second layer of skin. The fixation principle has changed from relying on external force support to relying on the conformal fit between its own shape and the tissue surface, achieving a fundamental leap from rigid fixation to flexible fit.

[0014] Functional Integration: A polymethyl acrylate-polyvinyl alcohol composite film is formed on the surface of the amniotic membrane using a spraying technique. Polyvinyl alcohol is a hydrophilic polymer that forms a hydrogel-like film that is soft, oxygen-permeable, and smooth, providing excellent biocompatibility and comfort. Polymethyl acrylate is a hydrophobic polymer that provides the necessary mechanical strength and stability to the film, preventing it from dissolving too quickly in ocular fluid. The combination of the two achieves a balance between flexibility and moderate tension, allowing the device to fit snugly without curling due to excessive softness or creating pressure due to excessive hardness.

[0015] The beneficial effects of this invention are: Borderless design: This avoids the problems of displacement, foreign body sensation, and inability to wear by patients with shallow conjunctival sacs caused by framed devices, resulting in better fit and follow-through.

[0016] Sutureless implantation: eliminates secondary trauma, inflammatory response, and patient discomfort caused by sutures, and simplifies the surgical procedure.

[0017] Dual protection mechanism: After the amniotic membrane dissolves due to its biological effects such as promoting healing and anti-inflammation, the remaining polymethyl methacrylate-polyvinyl alcohol film is smooth and transparent, and can continue to act as a physical barrier to protect the cornea and prolong the treatment effect.

[0018] High biocompatibility: Polyvinyl alcohol is a common component of artificial tears, and polymethyl methacrylate is a common material for artificial lenses. Both are non-toxic to eye tissues and their safety is guaranteed.

[0019] It has broad clinical applicability: it is suitable for a variety of ocular surface diseases such as non-infectious corneal ulcers, chemical burns, and persistent epithelial defects.

[0020] This invention resolves the conflict between fixation and comfort: the borderless conformal fit design fundamentally eliminates the risk of displacement and foreign body sensation caused by borders. Fixation no longer relies on physical pressure or puncture of tissue, but rather on the natural adhesion of the interface and the containment of the anatomical structure, thus achieving unprecedented comfort while maintaining effective fixation. This is especially crucial for patients with shallow conjunctival sacs.

[0021] This invention resolves the contradiction between short-term and long-term protection. Its functional release mechanism is as follows: First stage (short-term): The amniotic membrane tissue exerts its core biological activity, promoting epithelial healing, anti-inflammation, and anti-scarring. Second stage (long-term): After the amniotic membrane completes its function, it dissolves naturally, and the polymethyl methacrylate-polyvinyl alcohol film it supports remains as a smooth, transparent physical barrier, protecting newly formed, delicate epithelial cells, preventing eyelid friction, maintaining a moist environment, and continuing to promote ocular surface stability. This principle enables a single device to achieve a seamless integration of bioactive therapy and physical barrier protection, extending the treatment window—something that traditional amniotic membrane patches or framed amniotic lenses cannot achieve.

[0022] This invention utilizes a combination of polymethyl methacrylate (PMMA) and polyvinyl alcohol (PVA). This composite system can form a corneal matrix-like structure with controllable performance, supporting the amniotic membrane while also being a safe ophthalmic material that integrates perfectly into the ocular surface microenvironment. This invention achieves a morphology that matches the ocular surface anatomy through in-situ molding and realizes sequential functional release through material composites. Ultimately, it provides a simple, safe, and patient-comfortable solution to a series of long-standing clinical challenges for ophthalmologists. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of a frameless amnioscope.

[0024] Figure 2 The amniotic membrane (mucosal side up) is laid flat on the surface of a model eye (simulating the shape of the human cornea) with a specific radius of curvature.

[0025] Figure 3 Stained corneal images showing the corneal epithelial healing time of rabbits in groups A and B. Detailed Implementation

[0026] To clearly illustrate the technical features of this solution, the following detailed implementation method will be used to explain the solution.

[0027] A frameless amnioscope device includes: an amniotic tissue layer and a thin film layer; The amniotic membrane tissue layer is formed and covers the surface of the model eye; A thin film layer formed by a mixed solution of polymethyl acrylate and polyvinyl alcohol is sprayed onto the surface of the amniotic membrane tissue layer. This amniotic membrane lens device requires no frame support and can be directly implanted into the conjunctival sac to cover the cornea. Furthermore, the biocompatible thin film layer remaining after the amniotic membrane dissolves still provides protection.

[0028] Preferably, the overall diameter of the device is 14 mm and the sagittal height is 6.2 ± 0.1 mm; the amniotic membrane tissue layer is a fresh amniotic membrane or a bioengineered amniotic membrane processed within 6 hours of ex vivo.

[0029] Example 1: The fabrication method of the rimless amniotic endoscope device includes the following steps:

[0030] Step 1: Take the placenta from a healthy mother. Within 4 hours after removal, detach the amnion in a 4°C clean bench. Rinse repeatedly with saline containing antibiotics (such as penicillin or streptomycin) until clean, and remove any remaining chorionic tissue.

[0031] Step 2: Lay the cleaned amniotic membrane tissue (mucosal side up) flat on the surface of a model eye (simulating the shape of the human cornea) with a specific radius of curvature, allowing it to adhere naturally.

[0032] Step 3: Weigh 3g of low molecular weight polymethyl acrylate (PMMA) and add it to 10mL of physiological saline. Stir in a 60℃ water bath to form a homogeneous emulsion. Separately weigh 0.4g of polyvinyl alcohol (PVA) and add it to 10mL of physiological saline. Stir in a 90℃ water bath until completely dissolved. Mix the two solutions thoroughly to ensure a final PMMA concentration of 1%.

[0033] Step 4: Using a spray gun, uniformly spray the mixed solution onto the amniotic membrane tissue on the surface of the model's eye at a constant pressure (0.2 MPa) and distance (15 cm), controlling the spraying speed, and air dry at room temperature to form a composite layer. Repeat this process 2-3 times to ensure uniform film thickness.

[0034] Step 5: Trim the perimeter of the amnion with a precision mold to finally produce a frameless amnion mirror with a diameter of 14.0mm and a sagittal height of 6.2mm±0.1mm.

[0035] Step Six: Place the amnioscope in sterile preservation solution (containing DMEM medium, glycerol, and antibiotics) and freeze at -20°C. Before use, sterilize by radiation with a cobalt-60 source (absorbed dose of 25 kGy).

[0036] The preservation solution was prepared with the following formulation: 49.9% glycerol, 35% RPMI-1640 medium, 10% fetal bovine serum, 5% DMSO, and 0.1% penicillin-drug combination (0.0375% streptomycin at 10 mg / ml and 0.0625% penicillin at 80,000 U / ml). Alternatively, it could be 49.9% glycerol, 22.5% DMEM, 2.5% fetal bovine serum, 25% albumin, and 0.1% penicillin-drug combination (0.0375% streptomycin at 10 mg / ml and 0.0625% penicillin at 80,000 U / ml).

[0037] Example 2: Preliminary clinical application of the frameless amnioscopic device The device of this invention was used on three patients with moderate corneal chemical burns.

[0038] How to use: Step 1: The patient sits upright, and one drop of oxybuprocaine hydrochloride eye drops is instilled into the conjunctival sac for surface anesthesia.

[0039] Step 2: After one minute, use an eyelid speculum to open the eyelids and rinse the rimless amniotic lens with 10mL of sterile saline to remove the surface preservation solution.

[0040] Step 3: Hold the edge of the amniotic lens with sterile ophthalmic forceps and gently insert it into the conjunctival sac to completely cover the corneal wound.

[0041] Step 4: Remove the eyelid opener, instruct the patient to gently close their eyelids and slowly rotate their eyeballs several times to ensure that the frameless amniotic lens device is fully in contact with the ocular surface.

[0042] Step 5: Under slit lamp observation, the amnioscope is centered and well-fitted.

[0043] Results: All patients reported no or only mild foreign body sensation after implantation, indicating good tolerance. The device adhered tightly under slit-lamp observation. After an average follow-up of one week, the corneal epithelium of all three patients had completely healed, with an average healing time of (6.0±0.5) days. After the amniotic membrane dissolved, the residual transparent membrane remained for approximately 3-4 days without causing any discomfort. It was easily removed under slit-lamp guidance using ophthalmic forceps, with no corneal damage observed.

[0044] After wearing an amniotic lens, its coverage extends completely to the entire conjunctiva and corneal surface, providing comprehensive protection for the ocular surface. The lens boundary precisely matches the edge of the conjunctival sac, forming a seamless, sealed structure that ensures no fluid leakage or intrusion of external contaminants. This design achieves full coverage of the entire ocular surface, eliminating any visual or physical blind spots and providing an ideal microenvironment for corneal repair. The amniotic membrane remains stable under the lens's support, with even and moderate tension distribution. This avoids localized pressure caused by excessive tightness and prevents wrinkles or displacement caused by looseness. The uniform tension allows the amniotic membrane to adhere tightly to the corneal surface, eliminating gaps and promoting epithelial cell migration and adhesion, accelerating wound healing. Simultaneously, the excellent fit ensures even tear distribution under the lens, maintaining ocular surface moisture, reducing friction and irritation, and significantly improving patient comfort and treatment outcomes.

[0045] The above embodiments demonstrate that the device of the present invention is easy to operate, well tolerated by patients, and can effectively promote corneal epithelial repair.

[0046] Example 3: Evaluation of the in vitro performance and biological efficacy of the frameless amnioscopic device This embodiment verifies the performance and safety of the device of the present invention through in vitro experiments.

[0047] 1. Material characterization: Scanning electron microscopy revealed a natural porous fibrous network structure on the surface of the amniotic membrane. Furthermore, a mixed solution of polymethyl acrylate and polyvinyl alcohol formed a continuous, dense, and smooth film on the amniotic membrane surface, tightly bonded to the amniotic layer.

[0048] Biological performance tests were performed on the amniotic membrane, including: cell adhesion experiments: corneal epithelial cells were cultured on the treated amniotic membrane surface, and their adhesion and growth were observed. Ideally, the amniotic membrane basement membrane should still support the growth and migration of epithelial cells; anti-inflammatory and anti-scarring experiments: the inhibitory effect of the amniotic membrane on pro-inflammatory factors was tested to ensure that its anti-inflammatory properties were not impaired; and transparency testing: the light transmittance of the treated amniotic membrane was measured using a spectrophotometer to ensure that its optical performance met clinical requirements.

[0049] Mechanical property testing: The tensile strength of the film was tested using a universal testing machine. The results showed that the tensile strength of the polymethyl acrylate and polyvinyl alcohol composite film of the present invention was (15.3±2.1) MPa, and the elongation at break was (180±15)%, which was significantly higher than that of the amniotic membrane alone (tensile strength of about 5-8 MPa), indicating that it has sufficient mechanical strength to maintain the shape of the ocular surface and resist the external force of eyelid blinking.

[0050] Optical performance testing: The average transmittance of the film in the visible light band (400-700 nm) was measured to be >95% using a UV-Vis spectrophotometer, proving that it has extremely high transparency and does not affect the patient's vision.

[0051] Cell compatibility and healing-promoting effects: Cytotoxicity assay: The cytotoxicity of the extract to human corneal epithelial cells (HCECs) was detected using the CCK-8 assay according to ISO 10993-5 standard. Results showed that, compared with the negative control group, the cell viability in the experimental group was greater than 98%, and no cytotoxicity was observed.

[0052] Cell scratch healing experiment: 24 hours after scratching, the corneal epithelial cell migration rate of the extract group of the device of the present invention was increased by about 45% compared with the blank culture medium control group (p<0.01), indicating that it can significantly promote epithelial cell migration and scratch closure.

[0053] Example 4: Evaluation of the therapeutic effect of the frameless amniotic lens device in a rabbit corneal injury model This embodiment verifies the in vivo effectiveness and safety of the device of the present invention through animal experiments.

[0054] Sixteen healthy adult New Zealand white rabbits were selected, and a rabbit corneal epithelial injury model was established using the ethanol method. They were randomly divided into two groups of eight rabbits (eight eyes) each. Group A (borderless amniotic lens group): A borderless amniotic lens was fitted to the left eye (see...). Figure 1Group B (framed amniotic lens group): The left eye wore a frameless amniotic lens. Corneal epithelial healing was observed at 0h and 3d post-surgery. Corneal fluorescein staining was performed under a slit lamp, and photographs were taken. Tears were collected from rabbit eyes at 0h, 3d, and 7d post-surgery to measure the concentration of inflammatory factors. Conjunctival hyperemia scores, amniotic membrane dissolution rate, and amniotic lens dislocation rate were recorded, and any mechanical damage to the cornea was observed.

[0055] The experimental results showed that, firstly, the corneal epithelial healing time in group A was similar to that in group B, as indicated by the results below. Figure 3 As shown in Table 1, there was no statistically significant difference between the groups, indicating that both groups of amniotic lenses effectively promoted corneal epithelial repair. Secondly, on postoperative days 3 and 7, the IL-6 levels in the tear film of group A were lower than those of group B, as shown in Table 1, and the difference was statistically significant. This suggests that the rimless amniotic lens causes less irritation to the ocular surface and can effectively reduce discomfort caused by the rim. Thirdly, the conjunctival hyperemia score of group A was significantly lower than that of group B, as shown in Table 2, and the difference was statistically significant, further confirming that the rimless design causes less irritation to the ocular surface. Fourth, by day 7 of the experiment, no obvious mechanical damage, bleeding, exudation, or granulation tissue proliferation occurred in Group A. One case showed amniotic membrane dissolution, with the remaining amniotic membrane well-fixed but dislocated outside the eye. The remaining amniotic membranes adhered well and did not dislocate. Therefore, the amniotic membrane dissolution rate was 12.5%, and the amniotic lens dislocation rate was 12.5%. No obvious mechanical damage, bleeding, exudation, or granulation tissue proliferation occurred in Group B. Three cases showed amniotic membrane dissolution, with the amniotic lens frame dislocated outside the eye in one case and remaining inside the eye in two cases. The remaining amniotic membranes adhered well and did not dislocate. Therefore, the amniotic membrane dissolution rate was 25.0%, and the amniotic lens dislocation rate was 37.5%. The above results indicate that the sutureless, frameless amniotic endoscope design combines good fit, tracking and biocompatibility, effectively avoiding the problems of easy displacement, obvious foreign body sensation and limited wearing for patients with shallow conjunctival sacs caused by traditional framed devices. At the same time, it simplifies the surgical procedure, improves treatment safety and patient comfort, and has good clinical application prospects.

[0056] Table 1: Comparison of IF-6 concentration (pg / mL) in rabbit tears at different time points after surgery ; Table 2: .

[0057] Of course, the above description is not limited to the examples above. Technical features not described in this invention can be implemented by or using existing technology, and will not be repeated here. The above embodiments and drawings are only used to illustrate the technical solutions of this invention and are not intended to limit this invention. This invention has been described in detail with reference to preferred embodiments. Those skilled in the art should understand that any changes, modifications, additions or substitutions made by those skilled in the art within the scope of this invention do not depart from the spirit of this invention and should also fall within the scope of protection of the claims of this invention.

Claims

1. A frameless amnioscopic device, characterized in that: include: Includes the amniotic tissue layer and the thin membrane layer; The amniotic membrane tissue layer is formed and covers the surface of the model eye; A thin film layer formed by a mixed solution of polymethyl acrylate and polyvinyl alcohol is sprayed onto the surface of the amniotic membrane tissue layer. This amniotic membrane lens device requires no frame support and can be directly implanted into the conjunctival sac to cover the cornea. Furthermore, the biocompatible thin film layer remaining after the amniotic membrane dissolves still provides protection.

2. The frameless amnioscope device according to claim 1, characterized in that: The device has an overall diameter of 14 mm and a sagittal height of 6.2 ± 0.1 mm; the amniotic membrane tissue layer is a fresh amniotic membrane or a bioengineered amniotic membrane processed within 6 hours of ex vivo.

3. A method for manufacturing the frameless amnioscopic device according to any one of claims 1 to 2, characterized in that: Includes the following steps: Step 1: Obtain fresh amniotic membrane tissue and perform chorionic villi removal and aseptic cleaning within 6 hours of extraction at 4°C. Step 2: Cover the surface of the model eye with the processed amniotic membrane tissue; Step 3: Prepare a mixed solution containing polymethyl acrylate and polyvinyl alcohol. Step 4: Spray the mixed solution onto the surface of the amniotic membrane tissue to form a composite layer with tension; Step 5: Trim the periphery of the amniotic membrane tissue to form a circular frameless amnioscope with a diameter of 14mm and a sagittal height of 6.2±0.1mm; Step 6: The obtained amnioscope is stored in a -20°C preservation solution for cryopreservation and then sterilized by cobalt-60 radiation.

4. The manufacturing method according to claim 3, characterized in that: The method for preparing the mixed solution includes: adding low molecular weight polymethyl acrylate at 30% by weight to physiological saline to form an emulsion, dissolving polyvinyl alcohol at 4% by weight in physiological saline, and then mixing the two solutions to make the final concentration of polymethyl acrylate in the mixed solution 1% by weight.

5. A method of using the frameless amnioscopic device according to any one of claims 1 to 2, characterized in that: Includes the following steps: Step 1: Administer topical anesthesia to the patient's ocular surface; Step 2: Use an eyelid speculum to open the eyelids and rinse the surface of the amniotic lens with sterile saline. Step 3: Use ophthalmic forceps to grasp the edge of the amniotic lens and implant it into the conjunctival sac to cover the cornea; Step 4: Gently close your eyes and rotate your eyeballs to make the amniotic lens fit against the surface of your eye; Step 5: Observe the bonding condition using a slit lamp; Step Six: After the corneal epithelium has repaired or the amniotic membrane has dissolved, remove the remaining membrane directly.

6. The method of use according to claim 5, characterized in that: Topical anesthesia was achieved using oxybuprocaine hydrochloride eye drops.

7. The method of use according to claim 5, characterized in that: The amniotic membrane should be removed after the corneal epithelium has fully repaired or the amniotic membrane has dissolved.

Images