A sutureable composite artificial cornea and preparation method thereof

Abstract

The present invention discloses a sutureable composite artificial cornea and a preparation method thereof. The sutureable composite artificial cornea is obtained by mixing synthetic polymer materials and natural polymer biomaterials in a step-by-step or non-step-by-step manner to form an interpenetrating network structure between the two materials, thereby obtaining a firmly connected integrated artificial cornea. Synthetic polymer materials play a role in improving the biomechanical strength of the artificial cornea and the function of the corneal endothelium, so that the artificial cornea can withstand normal intraocular pressure, or even pathologically high intraocular pressure; natural polymer biomaterials are conducive to the attachment and growth of corneal epithelial cells and the growth of corneal stromal cells and nerve fibers; the radial structure composed of synthetic polymer materials in the peripheral area can withstand suture cutting and achieve normal suture; if corneal fixing wires are pre-placed, suture-free corneal transplantation can be achieved, which reduces the difficulty of the operation, simplifies the operation, and is suitable for doctors at all levels to perform the operation.

Description

Technical Field

[0001] The invention relates to the technical field of artificial corneas, and in particular to a sutureable composite artificial cornea and a preparation method thereof. Background Art

[0002] Corneal blindness is the second leading cause of blindness. According to WHO statistics, there are about 60 million patients worldwide, including about 5 million in my country, not including about 10 to 15 million people with corneal low vision (≤0.1). There are 100,000 new corneal blind people in my country each year, of which 70% are young and middle-aged people and 15% are children. These patients can regain their sight through corneal transplantation. Due to restrictions on corneal donations, less than 10,000 corneal blind patients are fortunate enough to receive corneal transplantation each year. Artificial corneas are an important way to solve the problems of insufficient sources of donated corneas and inability to guarantee quality.

[0003] Purely synthetic polymer materials, such as PHEMA and PMMA, are not suitable for cell growth, nor can they heal with human tissues or cells grow. They are currently mainly used to make contact lenses, artificial lenses, etc. Recently, corneal endothelial membranes made of synthetic polymer materials have been used for posterior lamellar keratoplasty to treat corneal endothelial lesions, but cannot be used for penetrating keratoplasty and cannot heal well with the patient's cornea.

[0004] Collagen-based artificial cornea is a very important artificial cornea at present, but it is far from reaching the optimal clinical standard. The main problem is that due to the weak biomechanical strength of collagen-based artificial cornea, it cannot tolerate intraocular pressure and suture cutting, so it can only be used for lamellar corneal transplantation and can only be fixed by pressure suture. In addition, since collagen-based artificial cornea has no corneal endothelial cells, collagen-based artificial cornea is not suitable for penetrating corneal transplantation. In order to improve the biomechanical strength of collagen-based artificial cornea, many methods of changing the collagen formula have been disclosed. The biomechanical strength of the collagen-based artificial cornea modified by these methods will be improved. Not only is it still not suitable for conventional suture fixation, but the cornea can only be fixed by pressure suture. More importantly, this modified collagen-based artificial cornea, as its hardness increases, affects its close attachment and healing with the patient's cornea and the growth of recipient corneal stromal cells and nerve fibers, and cannot achieve physiological postoperative healing. An invention discloses a double-layered artificial cornea in which a collagen membrane is bonded to a synthetic polymer membrane, aiming to improve the biomechanical strength of the collagen artificial cornea by using the synthetic polymer membrane, but there is a problem that the double-layered membrane is easy to dissociate. The patent CN115645113A previously applied by the inventor discloses a composite artificial cornea and a preparation method thereof, specifically disclosing a method of using a spatial mosaic structure to partially solve this problem, but there is still a dissociation phenomenon when the intraocular pressure is extremely high, and the present invention can solve this problem. Summary of the invention

[0005] In view of the problem that the existing collagen-based artificial cornea has weak biomechanical strength and cannot withstand intraocular pressure and suture cutting force, the present invention discloses a sutureable composite artificial cornea and a preparation method thereof, which is made by mixing synthetic polymer materials and natural polymer biomaterials in different proportions, and using methods such as in-situ casting, fiber direct writing or 3D printing. The present invention has the following advantages: ① The synthetic polymer materials in the matrix improve the biomechanical strength of the artificial cornea, and the pure synthetic polymer materials on the back surface have the function of the corneal endothelium, so that the artificial cornea can withstand normal intraocular pressure, even pathological high intraocular pressure, and is suitable for penetrating keratoplasty; ② The pure natural collagen on the front surface is conducive to the growth of corneal epithelial cells, and the pure natural collagen in the matrix is ​​conducive to the growth of corneal stromal cells and nerves; ③ The interpenetrating network structure between the two materials avoids the deficiency that the double-layer membrane of the previous double-layer membrane structure artificial cornea is easy to dissociate; ④ The radial structure in the peripheral area can withstand the cutting force of the suture, avoiding the problem that the existing collagen-based cornea cannot be conventionally sutured.

[0006] The present invention is achieved through the following technical solutions:

[0007] A sutureable composite artificial cornea is provided. The sutureable composite artificial cornea is formed by mixing synthetic polymer materials and natural polymer biological materials to form an interpenetrating network structure between the two materials, thereby obtaining a firmly connected integrated artificial cornea. The sutureable composite artificial cornea is made by casting, fiber direct writing or 3D printing.

[0008] The composite artificial cornea disclosed in the present invention is obtained by mixing a natural polymer biomaterial solution with a synthetic polymer material solution in a stepwise or non-stepwise manner to obtain an artificial cornea integrating natural polymer biomaterial and synthetic polymer material. This interpenetrating network structure allows the two materials to be closely combined to avoid separation, and in particular can better play the role of natural polymer biomaterial and synthetic polymer material, and better solve the problem of insufficient biomechanical strength of collagen-based artificial cornea and poor postoperative healing of natural polymer biomaterial cornea.

[0009] The composite artificial cornea proposed by the present invention also has a series of refractive powers according to actual needs, and is suitable for simultaneously correcting the refractive error that already exists in the patient before the operation.

[0010] Preferably, the interpenetrating network structure is as follows: the mass proportion of synthetic polymer materials gradually transitions from 100% of the artificial cornea's posterior surface to 0% of the anterior surface, and the mass proportion of natural polymer biomaterials gradually transitions from 0% of the posterior surface to 100% of the anterior surface.

[0011] The stepped or non-stepless mixing method is specifically as follows: taking 3D printing as an example, a computer automatically controls the output amount of polymer material ink and natural polymer biological material ink, so that the mass proportion of the synthetic polymer material gradually transitions from 100% of the rear surface layer of the artificial cornea to 0% of the front surface layer, and the mass proportion of the natural polymer biological material gradually transitions from 0% of the rear surface layer to 100% of the front surface layer, and an interpenetrating network is formed between the two materials, and the step concentration of the stepped mixing is 5%-10%.

[0012] Computer-controlled Thousand Layer Pancake Casting Method (Step Mixing): Temporarily prepare a mixture of synthetic polymer materials with a step concentration of X% and natural polymer materials with a step concentration of (100%-X%), with the step concentration X being 5-10, to achieve an artificial cornea with an interpenetrating network structure of 0% synthetic polymer materials and 100% natural polymer biomaterials on the front surface, and 100% synthetic polymer materials and 0% natural polymer materials on the back surface.

[0013] Preferably, the synthetic polymer material is selected from one or more of silicone, synthetic polymer hydrogel and acrylic polymer, and the natural polymer biomaterial is selected from one or more of collagen, natural polymer hydrogel, silk protein and cellulose. The mass volume concentration of the collagen solution is 2.0 to 6.5 g / L. Air-drying is carried out under the conditions of humidity of 50% to 80% and temperature of 20° C. to 25° C. The collagen proposed in the present invention is preferably commercially available natural type I collagen extracted from animals.

[0014] Preferably, the acrylic polymer is polyhydroxyethyl methacrylate (PHEMA). Polyhydroxyethyl methacrylate is obtained by polymerization reaction with hydroxyethyl methacrylate (HEMA) as monomer, ethylene glycol dimethacrylate (EDMA) as cross-linking agent, ammonium persulfate aqueous solution (APS) as initiator, and tetramethylethylenediamine (TEMED) as catalyst. In the present invention, the polymerization reaction can adopt a variety of cross-linking agents, initiators, and catalysts, and there are well-known technical means in the art. In the present invention, the "polymerization reaction" used is understood according to the common knowledge in the art, and refers to the polymerization reaction carried out in a solution state by adding an initiator (and a catalyst) to a monomer or its solution. The polymerization reaction can adopt a variety of polymerization methods, including oxidative polymerization, thermal polymerization and photopolymerization. The present invention preferably prepares polyhydroxyethyl methacrylate (PHEMA) according to the preparation method disclosed in ZL201811116393.7.

[0015] Preferably, the composite artificial cornea is divided into a central area and a peripheral area, and a plurality of tunnels or solid columns parallel to the surface of the artificial cornea and arranged radially are provided in the peripheral area. The tunnels or solid columns extend to the peripheral edge of the peripheral area, and the material constituting the tunnels or solid columns may be other materials different from the synthetic polymer material of the grid support, or / and may be doped with tracers such as pigments.

[0016] The present invention uses synthetic polymer materials to make a plurality of radially arranged tunnels in the peripheral area of ​​the artificial cornea, parallel to the rear surface of the artificial cornea (for example, 0.1 to 0.2 mm deep from the rear surface of the artificial cornea), and opens at the peripheral edge of the peripheral area for surgical suturing of the artificial cornea to the corneal implant bed of the patient or pre-places corneal fixing wires for fixing the artificial cornea to the corneal implant bed of the patient.

[0017] Preferably, a corneal fixing wire for suture-free fixation is arranged in the tunnel. In the peripheral area of ​​the artificial cornea, the tunnel is made of synthetic polymer material and is used for suturing or pre-setting a suture-free guide wire to fix the cornea. This suture-free design can simplify the surgical operation.

[0018] Further preferably, the corneal fixation wire is made of stainless steel medical metal, synthetic polymer material or degradable absorbable polymer biomaterial, and a barb with a fishhook barb-like structure is provided at the secondary front end of the corneal fixation wire, and the front end is connected to the suture and the suture needle in sequence, which is used to guide and pull the corneal fixation wire through the tunnel and into the patient's corneal implant bed during surgery.

[0019] The present invention also protects a method for preparing the above-mentioned sutureable composite artificial cornea, comprising the following steps: using fiber direct writing to obtain a grid-like wax frame with gradually changing porosity, and placing it in a mold of the artificial cornea, pouring a synthetic polymer biomaterial liquid into the mold, prefabricating a grid-like support of the synthetic polymer material by a lost wax method, eluting free monomers, and then injecting a natural polymer material to obtain a sutureable composite artificial cornea with an interpenetrating network structure of the two materials.

[0020] Preferably, the grid structure of the prefabricated grid-like synthetic polymer material support is not uniform. From the back surface to the front surface of the artificial cornea, the grid wall gradually becomes thinner and the grid porosity gradually increases, so that the mass proportion of the synthetic polymer material gradually transitions from 100% of the back surface to 0% of the front surface, and the mass proportion of the natural polymer biomaterial gradually transitions from 0% of the back surface to 100% of the front surface.

[0021] Taking collagen as an example, the collagen is dissolved in a hydrochloric acid solution with a concentration of 0.01 mol / L, and water is added and stirred to obtain a collagen solution with a concentration of 2.0 to 6.5 g / L; the collagen solution is poured into the mold at 4°C, and then 0.1-0.5 wt% 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added to the collagen solution for cross-linking reaction to obtain an artificial cornea. The mass ratio of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide to N-hydroxysuccinimide is 1:1.

[0022] The artificial cornea in the lost wax method proposed by the present invention is based on the external dimensions of the human cornea as parameters. The fiber direct writing pre-produces a gradually changing mesh support, and the porosity gradually decreases from 95% on the front surface to 5% on the back surface. Then the synthetic polymer biomaterial is cast in the mesh support, and after solidification, the wax frame is melted and removed, and the residual monomers and other auxiliary agents are soaked in deionized water to remove them, and then the natural polymer material liquid is injected to obtain the artificial cornea.

[0023] Further preferably, the mass proportion of the synthetic polymer material gradually transitions from 100% of the rear surface layer to 0% of the front surface layer in a step ratio of 5%-10%, and the mass proportion of the natural polymer biomaterial gradually transitions from 0% of the rear surface layer to 100% of the front surface layer in a step ratio of 5%-10%.

[0024] The present invention also protects the preparation method of the above-mentioned sutureable composite artificial cornea, which includes the following steps: during 3D printing, the output amount of synthetic polymer material ink and natural polymer biological material ink is automatically controlled by a computer to form an interpenetrating network of the two materials, so that the proportion of the polymer material ink gradually transitions from 100% of the rear surface layer to 0% of the front surface layer, and the proportion of the natural polymer biological material ink gradually transitions from 0% of the rear surface layer to 100% of the front surface layer. At the same time, in the peripheral area, a number of pipes or solid columns parallel to the artificial cornea surface and arranged radially are established to obtain a sutureable composite artificial cornea.

[0025] Preferably, the mass proportion of the synthetic polymer material ink gradually transitions from 100% of the rear surface layer to 0% of the front surface layer in a step ratio of 5%-10%, and the mass proportion of the natural polymer biological material ink gradually transitions from 0% of the rear surface layer to 100% of the front surface layer in a step ratio of 5%-10%.

[0026] The curvature of the artificial cornea proposed by the present invention is consistent with that of the human cornea. By slightly changing the front-back curvature of the artificial cornea or the optical refractive index of the polymer material, different refractive powers can be obtained for personalized transplantation of patients.

[0027] The mesh wall of the synthetic polymer mesh support gradually becomes thinner from the rear surface to the front surface, so that the proportion of the cast natural polymer biomaterial gradually increases from the rear surface to the front surface, and when it reaches the front surface of the artificial cornea, the mass proportion of the natural polymer biomaterial is 100%. The synthetic polymer mesh support can also be designed as a solid structure with the back 3 / 4 thickness of the central area of ​​the artificial cornea being solid, and the front 1 / 4 being a grid structure, so that the front surface of the artificial cornea is 100% natural polymer biomaterial, and the entire layer of the peripheral area of ​​the artificial cornea is still in a mesh.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] 1. The artificial cornea with an integrated structure of natural polymer biomaterials and synthetic polymer materials disclosed in the present invention can better reflect the advantages of the two materials. The synthetic polymer material plays a role in improving the biomechanical strength of the artificial cornea and similar to the corneal endothelium, so that the artificial cornea can withstand normal intraocular pressure, even pathological high intraocular pressure, and because of the role of the corneal endothelium, it is suitable for penetrating keratoplasty. Natural polymer biomaterials are conducive to the adhesion and growth of surface cells and the growth of corneal stromal cells and nerve fibers in the matrix.

[0030] 2. The present invention expands the indications: the sutureable composite artificial cornea can be used for other corneal transplants of various procedures such as penetrating keratoplasty and lamellar keratoplasty.

[0031] 3. The radial structure of the peripheral area can withstand the cutting force of the sutures, solving the current problem that collagen-based artificial corneas cannot be sutured normally.

[0032] 4. Simplified surgery and reduced difficulty: The pre-set intracorneal fixation guide wire eliminates the suturing operation in artificial cornea fixation, and can realize suture-free corneal transplantation, which reduces the difficulty of surgery, simplifies the surgical operation, improves the efficacy, and is suitable for doctors at all levels to perform surgery.

[0033] 5. The interpenetrating network structure between the two polymer materials avoids the shortcoming of the previous double-layer membrane structure artificial cornea that is easy to dissociate. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 It is a schematic diagram of the mixing ratio of natural polymer biological materials and synthetic polymer materials in the method for preparing an artificial cornea of ​​the present invention;

[0035] Figure 2 is a schematic structural diagram of an artificial cornea according to Embodiment 2 of the present invention;

[0036] Figure 3 yes Figure 2 A local enlarged schematic diagram along the A line;

[0037] Figure 4 is a schematic diagram of the top view of the artificial cornea according to Example 2 of the present invention;

[0038] Figure 5 This is a schematic diagram of the integrated structure of a suture needle and suture thread according to Embodiment 2 of the present invention;

[0039] Explanation of the reference numerals: 1. Central area; 2. Peripheral area; 21. Corneal fixing wire; 22. Barb; 23. Suture; 24. Suture needle. DETAILED DESCRIPTION

[0040] The present invention is further described in detail below with reference to the examples. These examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples where specific conditions are not specified are generally based on conventional conditions in the art or conditions recommended by the manufacturer; the raw materials, reagents, etc. used, unless otherwise specified, are considered to be raw materials and reagents that can be obtained through commercial channels such as conventional markets.

[0041] Figure 1 The gradient of the mixing ratio of the synthetic polymer material and the natural polymer biomaterial is only an example, and those skilled in the art can determine the mixing mode of the synthetic polymer material and the natural polymer biomaterial according to actual conditions.

[0042] Example 1

[0043] This embodiment provides a composite artificial cornea, which is prepared by an in-situ casting method, comprising the following steps:

[0044] S1. Make a mold with reference to the external dimensions of the human corneal stent as parameters. In the mold, use wax to pre-make a wax mold with a porosity of 90% on the back surface and gradually decrease to 5% porosity on the front surface. According to the disclosure of ZL201811116393.7, cast 4mL of 99% anhydrous HEMA, 2mL of water, 20μL of EDMA, 200μL of 10% APS aqueous solution by mass fraction, and 100μL of TEMED, and perform polymerization reaction at room temperature to prepare the molding. During the preparation, mix the above ingredients evenly and add them to the mold to stand for 3 hours to obtain the molded PHEMA, and then wash with deionized water. After the wax is lost, a porous PHEMA scaffold with interconnected mesh is obtained, and the interval of the PHEMA interconnected mesh scaffold gradually becomes thinner from the back surface to the front surface. A collagen solution with a concentration of 4.5g / L is perfused into the PHEMA interconnected mesh scaffold at 4°C, and then 0.3wt% 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide of the collagen solution are added for cross-linking reaction, so that the proportion of natural polymer biomaterials gradually increases from the back to the front, and the step concentration of the step-by-step mixing is 5%, and the front surface of the artificial cornea is 100% natural polymer biomaterials. It can also be designed as a structure in which the back 3 / 4 of the central area of ​​the artificial cornea is non-mesh and the front 1 / 4 is meshed.

[0045] S2. Make a mold 2 with reference to the human cornea shape, and place the PHEMA mesh support in the mold 2. Inject a collagen solution with a concentration of 4.5 g / L and EDC / NHS into the mold 2 to obtain a sutureable composite artificial cornea.

[0046] The tensile strength of the sutureable composite artificial cornea ranges from 3 to 8 MPa, and the results of the biomechanical strength destructive test reach 128 mmHg and 48 hours of pressure resistance; the 10-0 nylon suture is pressure-resistant: the cornea will not be broken even if the suture breaks; the white light transmittance of the cornea reaches 96%.

[0047] Comparative Example 1

[0048] The materials currently used to make biological artificial corneas are decellularized corneal stroma and animal collagen. Since they do not have cells and are not real corneas, they can only be used for anterior lamellar corneal transplantation and cannot be used for penetrating corneal transplantation. The artificial cornea of ​​collagen and PHEMA composite disclosed in the present invention combines the advantages of both, that is, it has good biological strength and can be used for penetrating corneal transplantation by healing with the patient's corneal implant bed.

[0049] Comparative Example 2

[0050] The use of synthetic polymer materials, such as PHEMA, can only be used to make contact lenses. Corneal endothelial membranes made of other synthetic polymer materials can only be used for posterior lamellar keratoplasty to treat corneal endothelial diseases, but cannot be used for penetrating keratoplasty. The artificial cornea of ​​collagen and PHEMA composite disclosed in the present invention combines the advantages of both and can be used for penetrating keratoplasty.

[0051] Comparative Example 3

[0052] In order to improve the biomechanical strength of collagen membrane by using synthetic polymer material membrane, the prior art discloses an artificial cornea with a double-layer membrane structure in which collagen membrane is bonded to the surface of synthetic polymer membrane. However, the adhesion of the double-layer membrane is not firm and the two are easily dissociated.

[0053] The interpenetrating network space structure disclosed in the present invention is used to make an artificial cornea, so that the collagen component and the synthetic polymer component are fused 360 degrees, similar to the overlapping of each page of two books, which greatly improves the friction force, and the tensile strength ranges from 3 to 8 MPa. During the corneal pressure-resistant ring test, the structure remains intact at 128 mmHg for 48 hours; during the suture pressure-resistant damage test, the 10-0 nylon suture is broken, and the corneal structure remains intact. At the same time, because PHEMA forms a pure PHEMA film on the posterior surface of the cornea, it has the function of an endothelial membrane sheet and can be used for penetrating keratoplasty; the pure collagen thin layer on the anterior surface of the artificial cornea is conducive to the growth of corneal epithelial cells, avoiding artificial corneal pseudomembranes; the collagen components around the artificial cornea are conducive to the growth of stromal cells and nerve fibers of the patient's corneal implant bed into the artificial cornea, achieving true physiological healing.

[0054] Example 2

[0055] This embodiment provides a sutureable composite artificial cornea, comprising the following steps:

[0056] On the basis of Example 1, the artificial cornea is divided into a central area 1 and a peripheral area 2. In the peripheral area 2, polycaprolactone (PCL) is used to make a plurality of radially arranged channels, and the channels open at the outer peripheral edge of the peripheral area of ​​the artificial cornea, such as Figure 2-5 As shown, the number of pipelines can be determined according to actual needs and is not limited to Figure 4 The number of channels shown in the figure is preferably preset to 12 or 16 in this embodiment. During clinical suturing, due to the strength of PCL, the physician can use 10-0 nylon sutures to pass through the radially arranged PCL lumens or solid bodies and fix the artificial cornea to the patient's corneal implant bed by conventional suturing techniques.

[0057] The corneal fixing wire 21 can also be placed in the PCL lumen, and the barb 22 of the fishhook barb-like structure is provided at the secondary front end of the corneal fixing wire 21, and the front end is connected with the suture 23 and the sewing needle 24 in sequence, and the suture 23 and the sewing needle 24 protrude outside the peripheral edge opening of the peripheral area of ​​the artificial cornea. When the artificial cornea is fixed clinically, the sewing needle 24 is inserted into the corneal implant bed of the patient, and passes through the sclera surface, and the suture 23 is pulled to make the corneal fixing guide wire 21 enter the corneal implant bed of the patient until the barb 22 of the fishhook barb-like structure enters the corneal implant bed of the patient, and the suture 23 is buried under the conjunctiva, and the excess suture and sewing needle are removed. This suture-free artificial cornea can reduce the difficulty of surgery, simplify surgical operations, and shorten the operation time.

[0058] Comparative Example 4

[0059] The current collagen-based artificial cornea has low biomechanical strength and cannot be sutured conventionally. The cornea can only be fixed by suture with pressure stitches. In order to improve the biomechanical strength of collagen-based artificial corneas and make them suitable for conventional suture fixation, CN115463258A and ZL202111071337.8 proposed using polyethylene glycol-treated collagen to improve the biomechanical strength of the cornea. Although the strength of the cornea made of collagen-like proteins is nearly 20 times higher, it still cannot withstand the cutting force of sutures and can only be fixed by suture with pressure stitches.

[0060] Comparative Example 2

[0061] In order to achieve the conventional method of suturing collagen-based artificial cornea, ZL201910772854.4 proposed a method of adding a PCL ring to the edge of the collagen-based cornea and fixing the corneal graft by suturing the PCL. However, the PCL ring blocks the growth of corneal implant cells and nerves into the corneal graft, which is not conducive to the healing of the artificial cornea and the patient's cornea and is not suitable for clinical practice.

[0062] Example 3

[0063] The same as Example 1, except that the synthetic polymer material is silicone, and the natural polymer biomaterial is natural polymer hydrogel. The mass proportion of the synthetic polymer material gradually transitions from 100% of the rear surface layer of the artificial cornea to 0% of the front surface layer at a step ratio of 5%, and the mass proportion of the natural polymer biomaterial gradually transitions from 0% of the rear surface layer to 100% of the front surface layer at a step ratio of 5%.

[0064] Example 4

[0065] The same as Example 1, except that: the mass proportion of the synthetic polymer material gradually transitions from 100% of the back surface of the artificial cornea to 0% of the front surface in a step ratio of 10%, and the mass proportion of the natural polymer biomaterial gradually transitions from 0% of the back surface to 100% of the front surface in a step ratio of 10%.

[0066] The description of the above embodiments is only used to help understand the technical solution and core ideas of the present invention. It should be pointed out that for technicians in this technical field, several improvements and modifications can be made to the present invention without departing from the principles of the present invention. These improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A sutureable composite artificial cornea, characterized in that: The sutureable composite artificial cornea is prepared by mixing synthetic polymer materials and natural polymer biomaterials in a step-wise or non-step-less manner to form an interpenetrating network structure between the two materials, thereby obtaining a firmly connected integrated artificial cornea. The sutureable composite artificial cornea is prepared by casting, fiber direct writing or 3D printing. Specifically, the interpenetrating network structure comprises: the mass proportion of the synthetic polymer material gradually transitions from 100% of the posterior surface layer of the artificial cornea to 0% of the anterior surface layer, and the mass proportion of the natural polymer biomaterial gradually transitions from 0% of the posterior surface layer to 100% of the anterior surface layer.

2. The sutureable composite artificial cornea according to claim 1, characterized in that: The synthetic polymer material is selected from one or more of silicone and acrylic polymers, and the natural polymer biological material is selected from one or more of collagen, silk protein and cellulose.

3. The sutureable composite artificial cornea according to claim 2, characterized in that: The acrylic polymer is polyhydroxyethyl methacrylate.

4. The sutureable composite artificial cornea according to claim 1, characterized in that: The synthetic polymer material is a synthetic polymer hydrogel, and the natural polymer biological material is a natural polymer hydrogel.

5. The sutureable composite artificial cornea according to claim 1, characterized in that: The artificial cornea is divided into a central area and a peripheral area. The peripheral area is provided with a plurality of tubes or solid columns parallel to the artificial cornea surface and arranged radially. The tubes or solid columns are made of materials other than the above-mentioned interpenetrating network stent, or / and are doped with tracers.

6. The sutureable composite artificial cornea according to claim 5, characterized in that: A corneal fixing wire for suture-free fixation is arranged in the pipeline.

7. The sutureable composite artificial cornea according to claim 6, characterized in that: The corneal fixation wire is made of stainless steel medical metal, synthetic polymer material or degradable and absorbable polymer biomaterial. A barb with a fishhook-like barb structure is arranged at the secondary front end of the corneal fixation wire, and the front end is connected with the suture and the suture needle in sequence, which is used to guide and pull the corneal fixation wire through the pipe or solid column and enter the patient's corneal implant bed during the operation.

8. The method for preparing the sutureable composite artificial cornea according to claim 1, characterized in that: The method comprises the following steps: obtaining a grid-shaped wax frame with gradually changing porosity by fiber direct writing, placing the frame in an artificial cornea mold, pouring synthetic polymer biomaterial liquid into the mold, prefabricating a grid-shaped frame of synthetic polymer material by the lost wax method, eluting free monomers, and then injecting natural polymer material to obtain a sutureable composite artificial cornea with an interpenetrating network structure of two materials.

9. The method for preparing a sutureable composite artificial cornea according to claim 8, characterized in that: The grid structure of the prefabricated grid-like synthetic polymer material scaffold is not uniform. From the back surface to the front surface of the artificial cornea, the grid wall gradually becomes thinner and the grid porosity gradually increases, so that the mass proportion of the synthetic polymer material gradually transitions from 100% of the back surface to 0% of the front surface, and the mass proportion of the natural polymer biomaterial gradually transitions from 0% of the back surface to 100% of the front surface.

10. The method for preparing the sutureable composite artificial cornea according to claim 1, characterized in that: The method comprises the following steps: during 3D printing, a computer automatically controls the output of synthetic polymer material ink and natural polymer biomaterial ink to form an interpenetrating network of the two materials, so that the mass proportion of the polymer material ink gradually transitions from 100% of the rear surface layer to 0% of the front surface layer, and the mass proportion of the natural polymer biomaterial ink gradually transitions from 0% of the rear surface layer to 100% of the front surface layer. At the same time, a number of pipes or solid columns parallel to the artificial cornea surface and arranged radially are established in the peripheral area to obtain a sutureable composite artificial cornea.

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