WO2014021073A1 - Artificial cornea, and method for producing artificial cornea - Google Patents

Abstract

The present invention provides: an artificial cornea which can be formed in a desired thickness and can have a desired surface state on each of both surfaces thereof; and a method for producing an artificial cornea. Specifically, two cornea-forming surfaces (4) for forming an artificial cornea (1) are arranged so as to face each other. An artificial cornea formation base (2) thus produced is placed in an environment in which a biological tissue material exists. The artificial cornea (1) is formed between the cornea-forming surfaces (4). The artificial cornea (1) is so formed that both surfaces of the artificial cornea (1) fit the cornea-forming surfaces (4), respectively. The distance between the cornea-forming surfaces (4) is set properly. In this manner, the artificial cornea (1) having a desired thickness is formed. Each of the cornea-forming surfaces (4) is so formed as to have a smooth surface. Each of the both surfaces of the artificial cornea (1) is formed into a desired surface state such as a smooth surface state.

Description

Artificial cornea and method for producing artificial cornea

The present invention relates to an artificial cornea formed in an environment in which a living tissue material exists such as in a living body, and a method for producing an artificial cornea.

In general, one of the important causes of visual impairment is a disease that causes turbidity of the cornea. Among these corneal diseases, infection and trauma such as viruses and bacteria, hereditary corneal diseases, etc. are treated with the cornea. Requires transplantation.

For cornea transplantation, donor corneas registered and donated to the eye bank are used for corneal transplantation, but in Japan in recent years, the number of eyes donated is about 1000 per year, while the number of cornea transplants is about 1500 per year, The number of patients is said to be 2000 to 3000, and donor corneas imported from overseas are used for some corneal transplants. Furthermore, even if imported donor corneas are used, the countries where eye banks are established are limited to developed countries, and the eye banks are not established in the developing countries, and the cornea becomes incompatible with transplantation due to infection. There is a problem that it is often.

In this situation where donor cornea is insufficient, amniotic membrane may be transplanted instead of donor cornea, and corneal opacity is caused by infection, trauma, or inherited corneal disease. Endothelial cell damage is a limited disease, and good results have been obtained in the treatment of corneal parenchymal disorders centering on collagen fibers. Furthermore, in recent years, research on cultured corneas and other artificial corneas applying regenerative medical technology has been conducted, and these artificial corneas are particularly useful for corneal epithelial stem cells and corneal endothelial cells in which cell proliferation ability is important. Expected to be effective in treating diseases.

However, amniotic transplantation is a cross-transplantation, although it has the advantage of requiring secondary corneal transplantation due to limited transparency recovery of the amniotic transplantation part and being less likely to cause rejection. Therefore, the risk of infection cannot be excluded. Moreover, in order to employ the cultured cornea, it requires cell culture equipment and engineers having knowledge and techniques thereof, and, regarding other artificial corneas, those made of various materials have been studied, At present, no artificial cornea has been developed that is easy to produce and provides good long-term results.

On the other hand, it is conceivable to facilitate the formation of an artificial cornea by, for example, forming an artificial cornea made of connective tissue in a living body, and further, by forming the artificial cornea in the body of itself, The risk of subsequent infections and rejection can be expected to be extremely low.

In order to form an artificial cornea in vivo, a base material is embedded in the living body, a connective tissue is formed around it, and this is used as an artificial cornea. A technique similar to that for forming can be used. This method uses living body's self-defense reaction to form living tissue such as artificial blood vessels and artificial valves from living cells. A plurality of forming techniques have been reported (see Patent Documents 1 to 3). The self-defense reaction used in this method is a connective tissue mainly composed of fibroblasts and collagen when fibroblasts gradually gather around them when foreign objects such as thorns invade deep in the body. It is a reaction that attempts to isolate a foreign body in the body by forming a capsule of the body and covering the foreign body.

When an artificial cornea is formed by such a method, an artificial cornea having a desired shape and size can be formed by appropriately setting the shape and size of a base material as a foreign substance to be embedded in a living body. .

JP 2007-312821 A JP 2008-237896 A JP 2010-094476 A

However, when an artificial cornea is formed around a base material implanted in a living body, it is possible to appropriately set the shape and size of the base material and form an artificial cornea of a desired shape and size around the base. Although it is possible, the artificial cornea cannot be formed to a desired thickness. In addition, by appropriately setting the surface condition such as the smoothness of the substrate, the surface of the artificial cornea on the substrate side can be formed in a desired surface state, but the surface opposite to the substrate is desired. The surface state cannot be formed.

An object of the present invention is to provide an artificial cornea capable of forming an artificial cornea having a desired thickness and capable of forming both surfaces of the artificial cornea into a desired surface state and a method for producing the artificial cornea.

In order to achieve the above object, an artificial cornea according to the present invention is formed on the surface of a base material in an environment where a biological tissue material exists, and both surfaces of the artificial cornea are formed according to the surface of the base material. Is.

According to the above configuration, since both surfaces of the artificial cornea are formed to match the surface of the substrate, both surfaces of the artificial cornea are formed, such as forming the substrate surface on a smooth surface and forming both surfaces of the artificial cornea on a smooth surface. It can be set to a desired surface state, and the artificial cornea can be set to a desired thickness by appropriately setting the distance between the surfaces of the base material forming both surfaces of the artificial cornea. Furthermore, by forming both sides of the artificial cornea on the surface of the base material, it is possible to reach the part of the artificial cornea that is farthest from the base material surface, compared to the case where an artificial cornea is formed by matching one side with the base material surface. The distance can be shortened, the artificial cornea can be thickened and the density can be made uniform.

Here, the “biological tissue material” is a substance necessary for forming a desired biological tissue, such as fibroblasts, smooth muscle cells, endothelial cells, stem cells, ES cells, iPS cells, etc. Animal cells, various proteins (collagen, elastin), saccharides such as hyaluronic acid, and other various physiologically active substances existing in vivo such as cell growth factors and cytokines. The “biological tissue material” includes materials derived from mammals such as humans, dogs, cows, pigs, goats and sheep, birds, fish and other animals, or artificial materials equivalent thereto.

In addition, “in the environment where biological tissue material is present” means in vivo (for example, limbs, mammals such as humans, dogs, cows, pigs, goats, sheep, birds, fish, and other animals). It refers to an artificial environment containing a biological tissue material outside the living body of an animal), or subcutaneously in the waist, back or abdomen, or embedded in the abdominal cavity.

Alternatively, the artificial cornea may be formed in a spherical shape with the central portion swelled, and an excess portion around the artificial cornea may be removed.

According to this configuration, since the surplus portion around the artificial cornea is removed, the base material is provided with a pair of spherical portions that form both surfaces of the artificial cornea so that the artificial cornea matches the spherical shape of the eyeball to be transplanted. In addition to the spherical portion, a portion for holding a pair of spherical portions at a predetermined interval can be provided around the spherical portion, and the structure of the base material for forming the spherical artificial cornea can be simplified. .

In addition, the present invention is a base material that can be placed in an environment where a biological tissue material exists to form an artificial cornea on the surface of the base material, and the artificial cornea is formed so that both surfaces of the artificial cornea are formed on the base material surface. An artificial cornea-forming substrate is provided in which two cornea-forming surfaces that form a surface are provided to face each other.

According to this configuration, since the two cornea-forming surfaces are opposed to each other, an artificial cornea having a desired thickness can be formed by appropriately setting the interval therebetween. Moreover, since both sides of the artificial cornea are formed according to the substrate surface, both sides of the artificial cornea are formed in a desired surface state, such as forming the cornea-forming surface into a smooth surface and forming both surfaces of the artificial cornea into a smooth surface. can do. Furthermore, since an artificial cornea is formed between two opposing cornea-forming surfaces, a portion of the artificial cornea that is farthest from the cornea-forming surface than when an artificial cornea is formed outside the one cornea-forming surface. Can be shortened, and a thick and uniform artificial cornea can be formed. That is, it is possible to form an artificial cornea similar to the above-mentioned artificial cornea having a desired sufficient thickness, a uniform density, and both surfaces having a desired surface state.

The artificial cornea-forming substrate of the present invention is not particularly limited in terms of the shape of the cornea-forming surface, the entire structure of the substrate, etc. as long as the two cornea-forming surfaces are provided facing each other. Various types can be adopted depending on the shape of the artificial cornea to be formed.

For example, as the artificial cornea-forming base material, a plurality of plate-like base materials having a cornea-forming surface are provided at intervals, and the plurality of plate-like base materials can be separated from each other.

According to this configuration, since a plurality of plate-like base materials having a cornea-forming surface are provided at intervals, an artificial cornea can be formed in the gap between the plate-like base materials, and a plurality of sheets By disassembling the plate-like substrate, the artificial cornea formed between the plate-like substrates can be easily taken out.

Further, as another artificial cornea-forming base material having a different configuration, a pair of base materials having a cornea-forming surface is provided, and the cornea-forming surfaces of the pair of base materials are divided into a spherical convex surface and a central portion with a central portion swelled It is also possible to use a hollow spherical concave surface that is formed at a distance from each other so that the pair of base materials can be disassembled from each other.

According to this configuration, since the spherical convex surface and the concave surface are provided as a cornea-forming surface and spaced apart from each other, a spherical artificial cornea can be formed in the gap between the cornea-forming surfaces. The artificial cornea formed between the cornea-forming surfaces can be easily taken out by decomposing the base material.

Further, the distance between the two corneal forming surfaces is not particularly limited, but it is preferable to set the interval between the corneal forming surfaces to 0.1 mm to 2 mm.

According to this configuration, an artificial cornea having a sufficient thickness as a cornea can be formed, and the gap between the two cornea-forming surfaces is set at a sufficient interval for the connective tissue to enter. The artificial cornea having a uniform density can be formed by sufficiently reducing the distance from an arbitrary position to the corneal surface.

Further, the surface roughness of the cornea-forming surface is not particularly limited, but it is preferable to set the surface roughness of the cornea-forming surface to an arithmetic average roughness of 50 μm or less.

According to this configuration, since the surface of the cornea-forming surface is set to be smooth, the connective tissue is easily invaded to improve the connective tissue formation state, and both sides of the artificial cornea are set to be sufficiently smooth as the cornea. In addition, after the artificial cornea is formed, the artificial cornea can be easily peeled off from the cornea-forming surface.

The present invention also provides a method for producing an artificial cornea using the artificial cornea-forming substrate. That is, in the method for producing an artificial cornea according to the present invention, an artificial cornea-forming substrate is placed in an environment where biological tissue material is present, and a connective tissue is formed around the artificial cornea-forming substrate, A forming step of forming a connective tissue between the corneal forming surfaces facing each other, a step of taking out the artificial corneal forming substrate coated with the connective tissue from the environment, and a corneal forming surface from the artificial corneal forming substrate. And a separation step of peeling the connective tissue between them to take out as an artificial cornea. Furthermore, in the separation step, after the connective tissue around the artificial cornea-forming substrate is removed, the artificial cornea-forming substrate is disassembled and the artificial cornea is taken out.

According to this configuration, the same effect as that obtained by adopting the configuration of the artificial cornea-forming base material can be obtained. In the present invention, any of autotransplantation, allotransplantation, and xenotransplantation may be used for the transplant recipient, but autotransplantation or allotransplantation is preferable from the viewpoint of avoiding rejection. In the case of xenotransplantation, it is preferable to perform an immunogen removal process such as a known decellularization process in order to avoid rejection.

Furthermore, in the installation step, a biological tissue material that promotes the formation of connective tissue may be accommodated between the corneal formation surfaces facing each other. Here, the biological tissue material that promotes the formation of connective tissue is, for example, blood, fat, collagen, gelatin, and those containing a growth factor or the like.

According to this configuration, since the biological tissue material that promotes the formation of connective tissue is accommodated between the corneal formation surfaces, the connective tissue grows and gradually enters the space between the corneal formation surfaces. The time required for the tissue formation can be shortened and the tissue formation can be made more reliable than waiting for the above.

In addition, by providing means for promoting the formation of connective tissue on the artificial cornea-forming substrate, the mechanical properties and components of the artificial cornea are improved, and a good-quality artificial cornea is formed in a relatively short time. Also good. Specifically, the artificial cornea-forming base material is provided with an LED that can promote the formation of connective tissue, and a drug container that stores and gradually releases a drug that can promote the formation of connective tissue. An example of such a configuration can be given.

As described above, according to the present invention, the two cornea-forming surfaces are opposed to each other, and the artificial cornea is formed by aligning both surfaces thereof with the surface of the substrate. Therefore, by appropriately setting the interval between the cornea-forming surfaces, It is possible to obtain an artificial cornea having a desired surface state such as a thickness, a smooth surface on both sides, a sufficient thickness, and a uniform density.

Photograph showing an artificial cornea according to the present invention Photograph showing cut surface of artificial cornea Perspective view of base material for artificial cornea formation Photo showing connective tissue formed on the substrate surface It is the photograph which shows the artificial cornea transplanted to the eyeball, (a) 1 day after transplant, (b) 5 days after transplant, (c) 15 days after transplant. A perspective view of an artificial cornea-forming substrate having a spherical cornea-forming surface A photograph showing the connective tissue formed on the surface of the artificial cornea-forming substrate of FIG.

Hereinafter, an embodiment of the artificial cornea and the method for producing the artificial cornea according to the present invention will be described with reference to the drawings.

The artificial cornea 1 shown in FIGS. 1 and 2 is obtained by separating the connective tissue formed on the surface of the artificial cornea-forming substrate 2 from the surface of the substrate in an environment where a biological tissue material exists, and has a desired shape. It is cut and used for corneal transplantation. The artificial cornea 1 is formed in a state where both surfaces thereof are in contact with the base material surface, is formed to have a desired thickness, a sufficient thickness, and a uniform density, and further, both surfaces are formed smoothly. .

As shown in FIG. 3, the artificial cornea-forming substrate 2 is for placing the artificial cornea 1 on the surface of the substrate by placing it in an environment in which a biological tissue material exists. 3a and 3b are provided at a distance from each other, and the two opposing surfaces of the two plate- like base materials 3a and 3b form the artificial cornea 1 so that both surfaces of the artificial cornea 1 are formed on the base material surface. The cornea forming surface 4 is formed.

The plate- like base materials 3a and 3b are rectangular plates having the same shape, which are slightly curved, and are arranged in a positional relationship in which they are moved parallel to each other in the thickness direction of the central portion, and can be separated from each other via the connecting portions 5 at the four corners. Is integrated. The coupling portion 5 is formed in a cylindrical shape with a small diameter, and by appropriately setting the length thereof, the pure interval between the plate- like substrates 3a and 3b, which is the interval between the cornea forming surfaces 4, is set. By cutting the plate- like base materials 3a and 3b.

The shape, size, and pure interval of the plate- like base materials 3a, 3b are set according to the shape, size, and thickness of the artificial cornea 1 to be formed. For example, the interval between the two cornea-forming surfaces 4 Is set to 0.1 mm to 2 mm. Furthermore, the surface state of the cornea-forming surface 4 is set according to the surface state such as smoothness to be formed of the artificial cornea 1. For example, the surface roughness of the cornea-forming surface 4 is an arithmetic average roughness of 50 μm or less. Is set. In addition, as long as there are a plurality of plate-like substrates, the number of plate-like substrates is not limited to two, and may be three or more. May be formed.

The material composing the artificial cornea-forming substrate 2 is not particularly limited, but strength (hardness), chemical stability, and sterilization that can prevent deformation due to implantation in a living body. Resins that have resistance to load and satisfy the condition that there is little or no eluate that stimulates the living body are preferable, and silicone resins and acrylic resins can be exemplified.

Next, a method for producing an artificial cornea using the artificial cornea-forming substrate as described above will be described.

This production method includes an “installation step” in which the artificial cornea-forming substrate 2 is placed in an environment where biological tissue material exists, and a cornea that faces each other while forming a connective tissue around the artificial cornea-forming substrate 2. “Formation step” of forming connective tissue between the formation surfaces 4, “Extraction step” of taking out the artificial cornea-forming substrate 2 covered with connective tissue from the environment, and cornea from the artificial cornea-forming substrate 2 It consists of a “separation step” in which the connective tissue between the formation surfaces 4 is peeled off and taken out as an artificial cornea 1.

<Installation process>
Biological tissue materials that promote the formation of connective tissue, such as blood, fat, collagen, gelatin, and those containing growth factors, etc., between the opposing corneal forming surfaces 4 of the artificial cornea-forming substrate 2 And the artificial cornea-forming substrate 2 is placed in an environment in which a biological tissue material exists. The environment in which the biological tissue material exists includes in an animal's living body (for example, subcutaneously or intraperitoneally embedded) or in an artificial environment such as a solution in which the biological tissue material floats outside the animal's body. . As biological tissue materials, materials derived from other mammals such as humans, dogs, cows, pigs, goats, rabbits, sheep, birds, fish, other animals, or artificial materials can also be used.

When embedding the artificial cornea-forming substrate 2 in an animal, it is performed with a minimum of incision under sufficient anesthesia, and the wound is sutured after implantation. As an implantation site | part of the base material 2 for artificial cornea formation, the intraperitoneal cavity which has the volume which receives the base material 2 for artificial cornea formation, or subcutaneous, such as an extremity part, a shoulder part or a back part, an abdomen, is preferable. In addition, when the artificial cornea-forming substrate 2 is placed in an environment in which a biological tissue material is present, cell culture may be performed according to a known method in a clean environment with various culture conditions.

<Formation process>
After a predetermined time has elapsed after the installation step, a film-like connective tissue is formed around the artificial cornea-forming substrate 2, and the connective tissue grows to form a cornea of the plate- like substrates 3a and 3b. It is formed so as to penetrate between the surfaces 4. The connective tissue is composed of an extracellular matrix such as fibroblasts and collagen, and is formed to a thickness corresponding to the pure interval between the plate- like substrates 3a and 3b.

Moreover, since the biological tissue material which accelerates | stimulates formation of a connective tissue is accommodated between the cornea formation surfaces 4 at the installation process, it gradually enters into the space between the cornea formation surfaces 4 while the connective tissue grows. The time required for the tissue formation is shortened and the tissue formation is more reliably performed than waiting for the going.

<Removal process>
After the connective tissue is sufficiently formed through the formation process for a predetermined time, an extraction process of taking out the artificial cornea-forming substrate 2 from the environment where the biological tissue material exists is performed. The artificial cornea-forming substrate 2 taken out from the environment in which the biological tissue material exists is entirely covered with a membrane made of connective tissue (see FIG. 4).

<Separation process>
The connective tissue around the artificial cornea-forming substrate 2 is removed, the joint portions 5 at the four corners are cut, and the artificial cornea-forming substrate 2 is disassembled into two plate- like substrates 3a and 3b. Remove 1 and remove. This artificial cornea 1 has a high quality and uniform density in the shape, size, thickness and surface state corresponding to the curved surface shape, size, pure interval and smoothness of the cornea-forming surface 4 of the plate- like substrates 3a, 3b. (See FIGS. 1 and 2).

When the produced artificial cornea 1 is xenotransplanted, it is preferable to perform immunogen removal treatment such as decellularization treatment, dehydration treatment, and fixation treatment in order to prevent rejection after transplantation. Examples of decellularization include ultrasonic treatment, surfactant treatment, and enzyme treatment such as collagenase to elute and wash the extracellular matrix. Dehydration methods include methanol, ethanol, isopropyl alcohol, etc. There is a method of washing with a water-soluble organic solvent, and as a method of fixing, there is a method of treating with an aldehyde compound such as glutaraldehyde or formaldehyde.

Next, how the artificial cornea is produced using the artificial cornea-forming base material and production method described above will be specifically described.

First, the artificial cornea-forming substrate 2 shown in FIG. 3 is implanted subcutaneously in the back of a 10 kg beagle dog, and the beagle dog is bred for 1 month under normal breeding conditions, and then covered with a connective tissue. The forming substrate 2 was extracted (see FIG. 4). The artificial cornea-forming substrate 2 is made of sterilized acrylic, and the pure interval between the plate- like substrates 3a and 3b is 0.5 mm.

The connective tissue formed under the skin is mainly composed of fibroblasts and collagen, encapsulates and covers the periphery of the artificial cornea-forming substrate 2, and penetrates between the cornea-forming surfaces 4 to form the artificial cornea 1. Was. In addition, the artificial cornea-forming substrate 2 covered with the connective tissue film could be easily removed from the subcutaneous tissue.

Next, the connective tissue around the artificial cornea-forming substrate 2 was peeled off to separate the plate- like substrates 3a and 3b, and the internal artificial cornea 1 was taken out (see FIG. 1). The cornea-forming surfaces 4 of the plate- like substrates 3a and 3b and the artificial cornea 1 were not adhered at all, and they could be easily separated without damage.

The thickness of the artificial cornea 1 was 0.47 ± 0.2 mm, which was the same thickness as the pure interval (0.5 mm) between the plate- like substrates 3a and 3b (see FIG. 2). In addition, both surfaces of the artificial cornea 1 were in the same smooth state as the cornea-forming surface 4 and had a substantially uniform density over all parts in the thickness direction (see FIG. 2). Thus, by forming the artificial cornea 1 between the cornea-forming surfaces 4 of the plate- like substrates 3a and 3b, the artificial cornea 1 having a desired shape, size, thickness, and surface state can be obtained. In addition, it can be seen that the density of the artificial cornea 1 can be made substantially uniform over the entire range in the thickness direction.

Next, a transplantation experiment was performed in which the cornea was superficially cut to form a defect in the eyeball, and the produced artificial cornea 1 was transplanted into the defect and observed for engraftment in the eyeball.

Specifically, first, a beagle dog (male, 8 years old) weighing 10 kg was given general anesthesia, and Baron's vacuum cornea trepan (diameter 6 mm) was used to make the beagle dog cornea up to a depth of 0.375 mm. An incision was made, and then the cornea was delaminated using a spatula, whereby a corneal surface resection with a diameter of 6 mm and a depth of 0.375 mm was performed to form a defect in the eyeball.

Furthermore, an artificial cornea 1 (transplanted biosheet) cut into a circle of 6.5 mm in diameter using a Baron donor corneal punch (6.5 mm in diameter) was transferred to a 10-0 nylon in the defect portion after resection of the corneal surface of a beagle dog. Suture was performed using a thread (see FIG. 5A). After transplantation surgery, antibiotics were instilled and administered for the prevention of infection and NSAIDs were administered systemically for analgesia, but no anti-inflammatory drugs or immunosuppressants were used.

After the transplantation of the cornea, the engraftment and transparency of the artificial cornea 1 on the cornea was observed. As a result, the transplanted artificial cornea 1 was cloudy immediately after the transplantation (FIG. 5 (a)). It gradually became transparent from the peripheral edge (FIG. 5 (b)), and almost 15 days after transplantation, almost the entire artificial cornea 1 became transparent (FIG. 5 (c)). No corneal neovascularization suggesting rejection was observed.

In addition, this invention is not limited to said embodiment, A change can be suitably added within the scope of the present invention. For example, the artificial cornea-forming substrate 2 has a structure in which the connecting portions 5 are provided at the four corners of the plate- like substrates 3a and 3b and the openings into which the connective tissue enters are provided on the four sides. The present invention is not limited to all having openings, but may be any having openings on at least one of the four sides.

Further, instead of the artificial cornea-forming substrate 2 composed of the plate- like substrates 3a and 3b, as shown in FIG. 6, an artificial cornea-forming substrate 6 that forms a spherical artificial cornea may be adopted. it can.

The artificial cornea-forming substrate 6 is formed on a pair of substrates 7a and 7b as a cornea-forming surface, a spherical convex surface 8 having a bulged central portion and a spherical concave surface 9 having a concave central portion. It is provided at intervals. Around the convex surface 8 and the concave surface 9, flat peripheral portions 10a and 10b are provided, and the peripheral portions 10a and 10b are connected via a plurality of connecting portions 11, so that the pair of base materials 7a and 7b are mutually connected. It is integrated so that it can be disassembled.

This artificial cornea-forming substrate 6 is placed in the living body of an animal and the like to form a connective tissue on the surface of the substrate, like the artificial cornea-forming substrate 2 (see FIG. 7). By removing the surrounding connective tissue, cutting the connecting portion 11 and breaking it into the base materials 7a and 7b, the artificial cornea between the convex surface 8 and the concave surface 9 can be peeled off and taken out. Furthermore, by removing an excess portion around the extracted artificial cornea, a spherical artificial cornea having a swelled central portion so as to match the eyeball shape can be obtained.

Moreover, it is necessary to form a connective tissue by providing an LED capable of promoting the formation of connective tissue, or forming a drug containing portion that contains a drug capable of promoting the formation of connective tissue and gradually releases it. While shortening time, you may make it obtain the connective structure | tissue where mechanical property and a component are favorable.

DESCRIPTION OF SYMBOLS 1 Artificial cornea 2 Artificial cornea formation base material 3a, 3b Plate-shaped base material 4 Cornea formation surface 5 Bonding part 6 Artificial cornea formation base material 7a, 7b Base material 8 Convex surface 9 Concave surface 10a, 10b Peripheral part 11 Connection part

Claims (9)

1. An artificial cornea formed on the surface of a base material in an environment where a biological tissue material exists, wherein both surfaces of the artificial cornea are formed according to the surface of the base material.
2. 2. The artificial cornea according to claim 1, wherein a central portion is formed in a swelled spherical shape, and an excess portion around the artificial cornea is removed.
3. Two surfaces on which an artificial cornea is formed so that both surfaces of the artificial cornea can be formed in accordance with the surface of the substrate, the substrate being capable of forming an artificial cornea on the surface of the substrate by being placed in an environment where biological tissue material exists An artificial cornea-forming substrate characterized in that the cornea-forming surfaces are provided to face each other.
4. The artificial cornea according to claim 3, wherein a plurality of plate-like base materials having the cornea-forming surface are provided at intervals, and the plurality of plate-like base materials can be disassembled with each other. Forming substrate.
5. A pair of base materials having the cornea-forming surface is provided, and the cornea-forming surfaces of the pair of base materials are formed into a spherical convex surface having a bulged central portion and a spherical concave surface having a concave central portion, and The artificial cornea-forming substrate according to claim 3, wherein the artificial cornea-forming substrate according to claim 3, wherein the artificial cornea-forming substrate is provided at an interval, and the pair of substrates can be separated from each other.
6. 6. The artificial cornea-forming substrate according to claim 3, 4 or 5, wherein an interval between the two cornea-forming surfaces is set to 0.1 mm to 2 mm.
7. The artificial cornea-forming base material according to any one of claims 3 to 6, wherein the surface roughness of the cornea-forming surface is set to an arithmetic average roughness of 50 µm or less.
8. An installation step of placing the artificial cornea-forming substrate according to any one of claims 3 to 7 in an environment in which a biological tissue material is present, and forming a connective tissue around the artificial cornea-forming substrate, A forming step of forming a connective tissue between opposing corneal forming surfaces, a step of taking out the artificial cornea-forming substrate covered with connective tissue from the environment, and the cornea from the artificial cornea-forming substrate. Separating the connective tissue between the forming surfaces and taking it out as an artificial cornea, and
   In the method for producing an artificial cornea, the separation step includes removing the connective tissue around the artificial cornea-forming substrate, and then decomposing the artificial cornea-forming substrate and taking out the artificial cornea.
9. The method for producing an artificial cornea according to claim 8, wherein in the installation step, a biological tissue material that promotes the formation of connective tissue is accommodated between the cornea-forming surfaces facing each other.

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