A flexible piezoelectric corneal contact lens for repairing corneal damage

Abstract

The purpose of the present invention is to provide a flexible piezoelectric corneal contact lens for repairing corneal damage, which belongs to the field of biomedical device technology. While avoiding secondary corneal damage caused by eyelid friction, the corneal contact lens converts the energy of daily blinking mechanical motion into an external electric field through a piezoelectric electret film, a rectifier and an electrode pair, thereby enhancing the endogenous electric field generated by the organism to repair the cornea. Without the need for external additional energy supply, it can achieve the effect of regulating the microenvironment of the damaged cornea, alleviating matrix fibrosis, promoting the orderly migration and regular arrangement of epithelial cells, alleviating corneal limbal stem cell deficiency, and restoring corneal clarity. At the same time, the core structure of the present invention, the piezoelectric electret film, adopts a 12-pointed star-shaped snowflake structure, which can effectively improve the robustness and stretchability of the structure, as well as the sensitivity and power generation density of the sensor.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical devices, and in particular relates to a flexible piezoelectric corneal contact lens for repairing corneal damage. Background Art

[0002] The cornea is a fragile tissue, and corneal injury is a common ophthalmic disease. Mild corneal injury can completely recover on its own; however, moderate or severe corneal injury can cause irreversible damage. The goal of corneal injury treatment is not only to physically close the wound, but more importantly, to orderly arrange the corneal tissue so that vision function can return to normal. The main clinical treatments for severe corneal injury include drug therapy, corneal transplantation, and stem cell therapy. Although some drug treatments can reduce stromal inflammation to achieve high corneal clarity, this approach is not conducive to promoting orderly tissue arrangement; corneal transplantation is an effective method for treating severe defective corneal diseases. Although the success rate is high, the demand for donor corneas increases and severe immune reactions cannot be avoided; in addition, cell therapy can effectively avoid rejection reactions and promote corneal repair, but it is still in the clinical stage and will prolong the treatment cycle. Therefore, how to repair corneal damage conveniently and efficiently is a challenge facing clinical medicine.

[0003] Endogenous electric field (EF) is an electric field that is spontaneously formed at the injured site after corneal injury, which can promote the orderly arrangement of tissues and the recovery of visual function. [1] However, the endogenous electric field has a limited ability to repair irreversible corneal damage. If no timely external intervention is given, it will lead to limbal stem cell deficiency (LSCD) with conjunctivalization and vascularization of the cornea. Strengthening the endogenous EF by applying external EF has been shown to effectively accelerate the orderly repair of the cornea. [2] However, equipment limitations and implementation complexity have hindered the widespread application of external EF. [3] . In addition, during the repair process of corneal damage, considering that humans naturally blink about 10,000 times a day, the friction between the eyelids and the cornea when blinking can cause secondary damage; and long-term eye closure treatment can cause problems such as hypoxia and edema, leading to further deterioration of the condition. Bandage contact lenses, as a clinical physical therapy method, have been widely used to avoid secondary damage caused by eyelid friction after corneal defects. However, their weak repair effect cannot accelerate the inherent corneal repair process or reduce the stromal inflammatory response. [4] .

[0004] Therefore, finding a safe and reliable way to drive corneal contact lenses to generate electric fields, thereby enhancing the ability of endogenous electric fields to repair the cornea, is the key to solving this problem.

[0005] [1] Zhao, M. et al. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTEN. Nature 442, 457-460 (2006).

[0006] [2]Tsai,RJF,Li,LM&Chen,JKReconstruction of damaged corneas bytransplantation of autologous limbal epithelial cells.N.Engl.J.Med.343,86-93(2000).

[0007] [3]Someya,T.,Bao,Z.&Malliaras,GGThe rise of plasticbioelectronics.Nature 540,379(2016).

[0008] [4] Blackmore, SJ The use of contact lenses in the treatment of persistent epithelial deficiencies. Cont. Lens Anterior Eye 33, 239-244 (2010). Summary of the Invention

[0009] To address the problems of the prior art, the present invention aims to provide a flexible piezoelectric contact lens for corneal repair. The contact lens utilizes piezoelectric sensing to convert mechanical blink energy into a unidirectional pulsed electric field, thereby enhancing the cornea's endogenous electric field and achieving corneal repair.

[0010] To achieve the above object, the technical solution of the present invention is as follows:

[0011] A flexible piezoelectric corneal contact lens for repairing corneal damage comprises, from top to bottom, a first outer packaging film, a first inner packaging film, a piezoelectric sensing layer, an electrode pair, a second inner packaging film, and a second outer packaging film;

[0012] The flexible piezoelectric contact lens further includes a rectifier, which is used to electrically connect the piezoelectric sensing layer and the electrode pair; the piezoelectric sensing layer is used to convert the energy generated during blinking into a pulse voltage signal, and the rectifier is used to convert the pulse voltage signal collected by the piezoelectric sensing layer into a direct current and output it to the electrode pair, which is used to convert the direct current signal into an external enhanced electric field to enhance the endogenous electric field;

[0013] The piezoelectric sensing layer is a piezoelectric electret film (PEG) with a 12-pointed star-shaped snowflake structure. The piezoelectric electret film consists of three layers, namely a top electrode layer, a middle organic material layer and a bottom electrode layer, which constitute a flat plate capacitor; the pattern of the electrode pair is two concentric circles, with a connecting line between the two concentric circles, and the circumference lines of the two circles and the connecting line are both serpentine lines.

[0014] Furthermore, the materials of the first outer packaging film and the second outer packaging film should be materials with good biocompatibility because they will be in direct contact with the eyeball, preferably 2-hydroxyethyl methacrylate (HEMA) with a thickness of 40-50 μm.

[0015] Furthermore, the first inner packaging film and the second inner packaging film are both made of polydimethylsiloxane (PDMS) with a thickness of 45-55 μm.

[0016] Furthermore, the material of the electrode pair is indium tin oxide (ITO) with a thickness of 90-110 nm.

[0017] Furthermore, the top electrode and the bottom electrode layers are made of metal aluminum, and the middle organic material layer is a polypropylene film.

[0018] Furthermore, the patterns of the piezoelectric sensing layer and the electrode pairs are formed by laser cutting.

[0019] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0020] The flexible piezoelectric contact lens designed by the present invention for corneal damage repair avoids secondary corneal damage caused by eyelid friction while converting the energy of daily blinking into an external electric field through a piezoelectric electret film, rectifier, and electrode pair. This enhances the endogenous electric field generated by the organism to repair the cornea. Without the need for external additional energy supply, it can achieve the effects of regulating the microenvironment of the damaged cornea, alleviating stromal fibrosis, promoting the orderly migration and regular arrangement of epithelial cells, alleviating limbal stem cell deficiency, and restoring corneal clarity. At the same time, the core structure of the present invention, the piezoelectric electret film, adopts a 12-pointed star-shaped snowflake structure, which can effectively improve the robustness and stretchability of the structure, as well as the sensitivity and power generation density of the sensor. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Schematic diagram of the structure of the flexible piezoelectric corneal contact lens of the present invention;

[0022] Among them, there are a first outer packaging film 1-1, a first inner packaging film 1-2, a piezoelectric sensing layer 1-3, a rectifier 1-4, an electrode pair 1-5, a second inner packaging film 1-6 and a second outer packaging film 1-7.

[0023] Figure 2 Schematic diagram of a human eye wearing the flexible piezoelectric corneal contact lens of the present invention.

[0024] Figure 3 Schematic diagram of the connection between the piezoelectric electret film, rectifier and electrode pair of the present invention.

[0025] Figure 4 This is a schematic diagram of the principle of generating an external electric field for the flexible piezoelectric corneal contact lens of the present invention.

[0026] Figure 5 This is a performance comparison chart of devices with different configurations in Example 1 and Comparative Example 1.

[0027] Figure 6 This is a diagram showing the therapeutic effect of the flexible piezoelectric corneal contact lens of the present invention being used to repair corneal damage in mice;

[0028] Among them, (a) is the comparison result of the corneal epithelial thickness of mice after 6 days, and (b) is the comparison result of the corneal clarity of mice after 6 days.

[0029] Figure 7 This is a diagram showing the therapeutic effect of the flexible piezoelectric corneal contact lens of the present invention being used to repair corneal damage in rabbits;

[0030] Among them, (a) is the comparison result of the rabbit corneal repair rate after 6 days, and (b) is the comparison result of the rabbit corneal clarity after 6 days. DETAILED DESCRIPTION

[0031] In order to make the objectives, technical solutions and advantages of the present invention more clear, the present invention is further described in detail below in conjunction with the implementation methods and drawings.

[0032] A flexible piezoelectric corneal contact lens for repairing corneal damage, the structural diagram of which is shown in FIG. Figure 1 As shown, from top to bottom are: a first outer packaging film 1-1, a first inner packaging film 1-2, a piezoelectric sensing layer 1-3, an electrode pair 1-5, a second inner packaging film 1-6, and a second outer packaging film 1-7;

[0033] The flexible piezoelectric contact lens also includes a rectifier 1-4, which electrically connects the piezoelectric sensing layer 1-3 and the electrode pair 1-5, and is used to convert the pulse voltage signal collected by the piezoelectric sensing layer 1-3 into a direct current and output it to the electrode pair 1-5; the piezoelectric sensing layer 1-3 is a piezoelectric electret film (PEG) with a 12-pointed star-shaped snowflake structure, and the piezoelectric electret film is composed of three layers, namely a top electrode layer, an intermediate organic material layer, and a bottom electrode layer, which constitute a flat plate capacitor. The top electrode and bottom electrode layers are metal aluminum, and the intermediate organic material layer is a polypropylene film. The piezoelectric sensing layer is used to convert the energy generated during blinking into a pulse voltage signal;

[0034] The pattern of the electrode pairs 1-5 is two concentric circles with a connecting line between the two concentric circles, and the circumference lines of the two circles and the connecting line are both serpentine lines.

[0035] Example 1

[0036] A method for preparing a flexible piezoelectric corneal contact lens for repairing corneal damage comprises the following steps:

[0037] Step 1. Prepare the piezoelectric sensing layer. The specific process is as follows:

[0038] Draw the desired pattern in CAD software, and then use femtosecond laser cutting technology to cut the piezoelectric electret film with double-sided aluminum electrodes into a 12-pointed star structure, that is, a regular 12-sided shape on a ring;

[0039] Step 2. Prepare the electrode pair. The specific process is as follows:

[0040] First, a polyethylene terephthalate film is adhered to a water-soluble tape. Next, an electrode pair pattern is drawn in CAD software. Then, the polyethylene terephthalate film adhered to the water-soluble tape is cut using femtosecond laser cutting technology to obtain an electrode pair with a pattern of two concentric circles with a connecting line between the two concentric circles. The circumferences of the two circles and the connecting line are both serpentine lines.

[0041] Step 3. Connect the piezoelectric sensor and the electrode pair. The specific process is as follows:

[0042] By using transfer printing technology and double-layer alignment marking technology, the piezoelectric sensing layer and electrode pair are sequentially adhered to the PDMS substrate with marking points, and then the water-soluble tape is removed; finally, the electrode pair, piezoelectric sensing layer and rectifier are welded together with a welding gun. The schematic diagram of the connection structure of the three is shown in FIG. Figure 3 As shown;

[0043] Step 4. Device packaging, the specific process is as follows:

[0044] Prepare an outer packaging film and an inner packaging film in the shape of a contact lens. First, package the structure obtained in step 3 with the upper and lower inner packaging films, and then package it with the upper and lower outer packaging films to obtain the required flexible piezoelectric corneal contact lens.

[0045] Among them, the biocompatibility of the outer packaging layer material should be good, and it is in direct contact with the eyeball. The inner packaging layer has good adhesion and is used to fix the piezoelectric sensing layer, electrode pairs and outer packaging layer. At the same time, the inner packaging layer uses PDMS material, which is impermeable to water and breathable. Therefore, the center of the inner packaging layer is partially hollow for water and breathability. Figure 1 The four small dots on the periphery of the inner and middle packaging layers are only marking points for alignment during the preparation process.

[0046] Schematic diagram of human eye wearing flexible piezoelectric corneal contact lens Figure 2 shown.

[0047] Comparative Example 1

[0048] A flexible piezoelectric corneal contact lens was prepared according to the steps of Example 1, except that the pattern structure of the piezoelectric sensing layer was adjusted to a four-pointed star structure, a six-pointed star structure, and an eight-pointed star structure, while other steps remained unchanged.

[0049] Figure 4 This diagram shows the principle behind the generation of an external electric field in the flexible piezoelectric contact lens of the present invention. The middle organic material layer (polypropylene) of the piezoelectric electret film (PEG) has a high piezoelectric coefficient. Upon polarization, multiple positive and negative charge pairs accumulate on the inner surface of the polypropylene lens-shaped air gap, forming macroscopic "quasi-dipoles." These "quasi-dipoles" generate a strong internal electric field and induce charges of opposite polarity in the aluminum electrode layer.

[0050] When the eye is in the process of daily blinking, the corresponding movement cycle of the PEG layer in the flexible piezoelectric corneal contact lens (BPCL) is as follows Figure 4As shown in (i)-(iv). When the eyes are fully open, the charge pairs stored within the PEG's intermediate organic material layer and the opposite charges induced on the PEG's aluminum electrodes are in electrostatic equilibrium, resulting in no voltage difference (VD) between the top aluminum electrode (TAE) and the bottom aluminum electrode (BAE) in the circuit (VD = 0, stage i). During eye closure, the distance between the top aluminum electrode (TAE) and the bottom aluminum electrode (BAE) decreases, and under the pressure of the upper and lower eyelids, the total thickness of the PEG layer decreases, thereby reducing the polarization strength of the macroscopic dipole and driving electrons to flow from TAE to BAE through the rectifier and the ITO electrode (VD > 0, stage ii). When the eyes are fully closed, the thickness of the PEG is minimized under the pressure of the eyelids, at which point the charge transfer reaches its maximum, the net current through the circuit drops to zero, and a new electrostatic equilibrium is established (VD = 0, stage iii). From the closed to the open stage (VD > 0, stage iv), the PEG gradually returns to its inherent elastic state, the total thickness of the air layer increases, causing the opposite electron flow from BAE to TAE until the eyes reach the initial open stage (i) again.

[0051] Figure 5 A performance comparison chart of devices made with different configurations. The open-circuit peak-to-peak voltage of PEG is defined as Vpp. Devices with 4, 6, 8, and 12 corners were designed, with corresponding Vpp values ​​of 1.0, 1.3, 1.5, and 2.5V, respectively. Due to the improved piezoelectric area, the 12-pointed star structure of PEG can improve sensitivity and power generation density. Furthermore, compared with other geometric configurations, comprehensive testing shows that PEG (12-pointed star) has the best overall performance, stretchability, and mechanical properties, based on a comprehensive evaluation of piezoelectric area, inscribed circle area, and voltage output.

[0052] The shape of the electrostatic electret film is determined by a combination of the device's area and sensitivity. Because the pupil area is fixed, the diameter of the inscribed circle of the piezoelectric sensing layer is limited, otherwise it would obstruct vision. Furthermore, the entire device area is also limited, so designing the shape of the piezoelectric sensing layer within the limited area of ​​the hollow ring is a key consideration. Fewer corners result in a smaller inscribed circle radius; however, more corners reduce the piezoelectric sensing layer's flexibility when stretched.

[0053] Figure 6The figure shows the therapeutic effect of the present invention on repairing corneal damage in mice. First, the right cornea of ​​the mouse was burned with NaOH for 10 seconds, and then the eyes were rinsed with 20 ml of normal saline to establish a corneal alkali damage model. Under the same experimental conditions, mice in the MI group (experimental group) wore the BPCL of the present invention for intervention treatment; mice in the MS group (sham experimental group) wore damaged BPCL for intervention treatment; and mice in the MB group (blank control group) did not receive intervention treatment. It can be seen from the figure that the flexible piezoelectric corneal contact lens has a significant repair effect on corneal damage in mice, specifically: the cornea of ​​the damaged area was collected on the 6th day of the experiment of wearing the contact lens, and microscopic observation was performed. Figure 6 (a) Comparison of corneal epithelial thickness in mice after 6 days. H&E staining analysis confirmed that the MI group achieved effective re-epithelialization at the injury site, while the MS and MB groups showed reduced epithelial thickness. Epithelial thicknesses in the normal (uninjured) and MI groups on day 6 were 39.10±2.16μm and 36.75±2.63μm, respectively, significantly greater than those in the control group (MS: 21.78±2.85μm, MB: 24.48±2.50μm). Figure 6 (b) Comparison of corneal clarity of mice after 6 days. The corneal opacity score of the MI group on day 6 was 0.50±0.58, which was smaller than that of the MS (1.75±0.5) and MB (1.75±0.58) groups, respectively.

[0054] Figure 7 The figure shows the therapeutic effect of the present invention on repairing rabbit corneal damage. First, the right cornea of ​​the rabbit was burned with NaOH for 10 seconds, and then the eyes were rinsed with 20 ml of normal saline to establish a corneal alkali damage model. Under the same experimental conditions, rabbits in the RI group (experimental group) wore BPCL for intervention treatment; rabbits in the RS group (sham experimental group) wore damaged BPCL for intervention treatment; and rabbits in the RB group (blank control group) did not receive intervention treatment. It can be seen from the figure that the flexible piezoelectric corneal contact lens has a significant repair effect on rabbit corneal damage. Specifically: on the 8th day of the experiment of wearing contact lenses, the cornea of ​​the damaged area was collected and observed under a microscope. Figure 7 (a) is the comparison of the corneal repair rate of rabbits after 6 days. The corneal repair rate of the RI group (experimental group) was 92.9±3.0%, which was significantly higher than that of the control group (RS (sham experimental group) was 40.0±7.8%, RB (blank control group) was 41.4±5.2%). Figure 7 (b) Comparison of corneal clarity of rabbits after 6 days. The opacity score of the RI group on the 8th day was 0.33±0.58, which was higher than that of the RS group (2.0) and the RB group (2.0).

[0055] The above description is only a specific embodiment of the present invention. Any feature disclosed in this specification, unless otherwise stated, can be replaced by other equivalent or alternative features with similar purposes; all disclosed features, or all steps in the methods or processes, except for mutually exclusive features and / or steps, can be combined in any way.

Claims

1. A flexible piezoelectric corneal contact lens for repairing corneal damage, characterized in that: From top to bottom: first outer packaging film, first inner packaging film, piezoelectric sensing layer, electrode pair, second inner packaging film, and second outer packaging film; The flexible piezoelectric contact lens further includes a rectifier, which is used to electrically connect the piezoelectric sensing layer and the electrode pair; the piezoelectric sensing layer is used to convert the energy generated during blinking into a pulse voltage signal, and the rectifier is used to convert the pulse voltage signal collected by the piezoelectric sensing layer into a direct current and output it to the electrode pair, which is used to convert the direct current signal into an external enhanced electric field to enhance the endogenous electric field; The piezoelectric sensing layer is a piezoelectric electret film with a 12-pointed star-shaped snowflake structure. The piezoelectric electret film consists of three layers, namely a top electrode layer, a middle organic material layer and a bottom electrode layer, which constitute a flat plate capacitor; the pattern of the electrode pair is two concentric circles, with a connecting line between the two concentric circles, and the circumference lines of the two circles and the connecting line are both serpentine lines.

2. The flexible piezoelectric contact lens according to claim 1, wherein: The first outer packaging film and the second outer packaging film are both made of 2-hydroxyethyl methacrylate, with a thickness of 40-50 μm.

3. The flexible piezoelectric contact lens according to claim 1, wherein: The first inner packaging film and the second inner packaging film are both made of polydimethylsiloxane, with a thickness of 45-55 μm.

4. The flexible piezoelectric contact lens according to claim 1, wherein: The material of the electrode pair is indium tin oxide with a thickness of 90-110nm.

5. The flexible piezoelectric contact lens according to claim 1, wherein: The materials of the top electrode layer and the bottom electrode layer are metal aluminum, and the material of the middle organic material layer is polypropylene film.

6. The flexible piezoelectric contact lens according to claim 1, wherein: The patterns of the piezoelectric sensing layer and the electrode pairs are both formed by laser cutting.

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