CN110025402B

CN110025402B - Artificial cornea containing biological material

Info

Publication number: CN110025402B
Application number: CN201910422471.4A
Authority: CN
Inventors: 王丽强; 黄一飞
Original assignee: Individual
Current assignee: Third Medical Center of PLA General Hospital
Priority date: 2019-05-21
Filing date: 2019-05-21
Publication date: 2021-09-24
Anticipated expiration: 2039-05-21
Also published as: CN110025402A

Abstract

The invention discloses a biomaterial-containing artificial cornea, which comprises an optical part and a biomaterial member, wherein the biomaterial member is made of biomaterial, and the biomaterial comprises autologous material and/or non-autologous material. The novel artificial cornea has good biocompatibility, optical performance and mechanical strength performance, is suitable for various complicated and serious corneal blindness and recurrence treatments, can utilize the autologous cornea of a patient and can also adopt a donor cornea as a carrier, and is convenient for large-scale popularization and use.

Description

Artificial cornea containing biological material

Technical Field

The invention relates to the technical field of medicines, in particular to a novel artificial cornea containing biological materials.

Background

According to the report of World Health Organization (WHO) in 2009, there are about 800 ten thousand patients with corneal blindness all over the world. About 300 million patients with corneal blindness exist in China. The penetrating corneal transplantation is the main vision recovery means for corneal blindness at present, and the low-risk lesion power can reach 70% in 5 years. However, the success rate of the method is below 50% for high-risk cases with a large amount of corneal neovascularization, and the like, and particularly, the success rate of the method is below 50% for unrecoverable eyelid or conjunctival sac dysfunction caused by severe scar, vascularization, infection or immune diseases of the cornea caused by chemical burns such as severe acid-base chemical burns, such as complete occluded eyelid adhesion, Steven-Johnson syndrome (SJS), Ocular Cicatricial Pemphigoid (OCP), and corneal blindness caused by multiple corneal transplantation failures with severe bed neovascularization, and the like, and corneal transplantation operations cannot be successful, which are clinically called as end-stage corneal blindness. Keratoprosthesis implantation is its only reconstructive means and method.

Artificial cornea (Kpro) is an artificial device for replacing a diseased cornea to exert its optical and biological functions, and is the final means for recovering patients with corneal opacity who cannot be recovered by corneal surgery. In order to achieve an ideal optical effect, the artificial cornea is mostly in a through type at present, namely, an optical part of the artificial cornea penetrates through the whole layer of the cornea, the optical part is fixed in the center of the cornea through a bracket, one of the most important clinical indexes of the artificial cornea is the in-situ ratio, various artificial corneas in the past can cause the discharge of the artificial cornea due to tissue dissolution infection, foreign body reaction and the like, and a certain gap is formed among the optical part of the artificial cornea, the peripheral bracket and a tissue structure. Clinically, potential cavities exist between the artificial cornea and surrounding tissues, biological combination cannot be achieved, the discharge risk of the artificial cornea is increased, the opportunity that microorganisms enter eyes is increased, and serious complications, namely infectious endophthalmitis, after the artificial cornea operation can be caused, so that the visual function is seriously threatened.

Research and application of keratoprostheses has been greatly advanced since the concept of keratoprostheses was proposed by Quengsy (1789). Currently, the internationally applied artificial corneas are: boston keratoprostheses type I, type II (Dohlman C, Harissi-Dagher M. digital J Ophalmol.2007; 13:3.), US patent 5354332A discloses keratoprosthesis skirt stents made of PMMA, a novel Boston KPro replaces the PMMA posterior disk with a titanium alloy posterior disk (Cruzat A. et al. Cornea.2013; 32(12):1531 and 1536.), as well as osseous-odontographostomatosis (OOKP) (Tan, X.W., et al. invest Ophthalmol Vis Sci,2011.52(1): p.21-9.) and Russian MICOF keratoprosthesis (Hunang, Y.et al. Ophtlmology, 2011.118(1): p.41-6.).

Although these materials can form stents, there are still more problems in practical applications. At present, most of the global application cases are Boston type I, the artificial cornea is made of PMMA materials, the indication is the case of multiple cornea transplantation failures, and severe complications such as corneal dissolution and the like are easy to occur for patients with end-stage corneal blindness due to poor tear and ocular surface conditions. Boston keratoprostheses require a corneal implant as a carrier. Boston keratoprostheses type II, OOKP and MICOF keratoprostheses are all suitable for end-stage corneal blindness, with OOKP keratoprostheses being best in situ rates, which have been maintained for more than 20 years at the maximum, and it is widely accepted by those skilled in the art that the abundant vascular supply of the dental bones is essential for the in-situ rates of keratoprostheses. However, the clinical popularization of the artificial cornea is limited by the factors that the bending strength of the used human teeth and bone tissues is low, the operation is difficult, the preparation is difficult, the operation is complicated, the supply area damage is large, the individual processing is required, the batch production cannot be realized, and the like. Hydrogel keratoprostheses lack sufficient compressive strength and are highly demanding of ocular and tear conditions and unsuitable for such patients. There is therefore still a need for a keratoprosthesis that overcomes the above-mentioned disadvantages.

Disclosure of Invention

In view of the above, there is still a great need in the art for an artificial cornea with good biocompatibility, good biomechanical properties, good flexural strength and compressive strength, and abundant sources.

The main purpose of the present invention is to overcome the above mentioned drawbacks of the existing artificial cornea, and to provide an artificial cornea containing biological material and an implantation method thereof, which are used to enhance the bio-integration of the artificial cornea, reduce the discharge of the artificial cornea during the use process, and reduce the incidence of infection.

In order to achieve the above objects, the present inventors have found through studies that a biomaterial selected from a non-autologous material, which is, for example, one or more of autologous materials such as autologous cartilage, non-autologous cartilage, bovine pericardium, tissue engineering materials, decellularized materials and polymer biomaterials, has a certain bioactivity and biomechanical properties, and when the biomaterial is used as a member in artificial cornea surgery, it is possible to reinforce the tissue around the artificial cornea against invasion such as tissue lysis and infection, enhance the bio-integration of the artificial cornea, and reduce the incidence of infection during the use of the artificial cornea.

The invention takes autologous material and/or non-autologous material as the reinforcing material of the artificial cornea, reduces foreign body reaction caused by the optical lens column, avoids the expansion of the gap between the optical lens column and the surrounding tissues in vivo for a long time, and the adjustable design of the fixed disk can ensure that the lens column is tightly connected with the surrounding tissues, and reduce the incidence rate of secondary intraocular infection caused by bacteria and other microorganisms entering eyes, thereby achieving better biocompatibility, mechanical strength and operation effect.

In order to achieve the purpose, the invention can adopt the following technical scheme:

one aspect of the present invention provides a biomaterial-containing artificial cornea comprising an optical portion and a biomaterial component, the biomaterial component being comprised of a biomaterial, the biomaterial comprising an autologous material and/or a non-autologous material.

By adopting the scheme, the biocompatibility of the artificial cornea can be improved, and gaps among the optical part, the peripheral bracket and the tissue structure can be eliminated, so that the infection incidence rate of the artificial cornea in the use process can be reduced, and the biological integration of the artificial cornea can be enhanced.

In a specific embodiment, the optical portion penetrates a patient's cornea when implanted therein, and the biomaterial element replaces the patient's cornea or is located on an anterior surface of the patient's cornea when implanted therein, wherein the fixation of the artificial cornea includes posterior-penetration anterior fixation and anterior-penetration posterior fixation.

In a specific embodiment, the optical part includes an optical lens column and another part connected to the optical lens column, the material of the another part is the same as or different from the material of the optical lens column, the optical part can perform an optical function after being implanted in a patient, the another part can perform a function of fixing the optical lens column, preferably, the another part includes a support table and/or a fixing table, the another part further includes an upper ring when the optical part is fixed in a back-wearing manner, and the another part further includes a latch when the optical part is fixed in a front-wearing manner.

In a preferred embodiment, the optical portion fixation is an adjustable fixation plate design. The adjustable fixing ring is a ring which can be adjusted according to the thickness of the cornea and tissues of a patient to fix the front and the rear discs, so that the gap of the artificial cornea caused by different conditions of the cornea of different patients is avoided.

In a specific embodiment, the autologous material is autologous cartilage, preferably autologous auricular cartilage, and the non-autologous material is any one or more of non-autologous cartilage, tissue engineering material, acellular material, composite stem cell chondrogenic bone and polymer biomaterial.

In a specific embodiment, the non-autologous cartilage is non-autologous auricular cartilage, the tissue-engineering material is tissue-engineered bone or cartilage, the decellularized material is decellularized bone tissue or cartilage tissue, and the composite stem cells used for chondrogenesis of the composite stem cells are stem cells of various origins, preferably mesenchymal stem cells, embryonic stem cells or induced pluripotent stem cells.

In a specific embodiment, the optical lens column is made of at least one material selected from the group consisting of poly (hydroxyethyl methacrylate), poly (methyl methacrylate), silicone gel, and glass, and preferably made of medical grade poly (methyl methacrylate) (PMMA).

In a specific embodiment, the optic cylinder replaces all or part of the original lamellar and/or full-thickness cornea of the patient when implanted in the cornea of the patient.

In a specific embodiment, the other portion is integrally formed with or connected to the optical lens column and functions to fix the optical lens column to the eye.

In a specific embodiment, the artificial cornea is a compound artificial cornea. The preferable scheme is that the composite artificial cornea comprises an optical lens column with threads, a supporting table connected with the optical lens column into a whole, a fixed disc capable of being in threaded connection with the threads on the optical lens column, and an upper ring and/or a locking ring.

Another aspect of the invention provides the use of a biomaterial for the preparation of an implant for the treatment of corneal blindness.

ADVANTAGEOUS EFFECTS OF INVENTION

The invention has the advantages that the biological material is used as the artificial cornea component, the inflammatory reaction is slight, the foreign body reaction caused by the optical part is reduced, and the aim of biological integration of the optical part and the surrounding tissues is achieved, thereby increasing the long-term stability and the in-situ rate of the human cornea, reducing the gap between the optical part and the surrounding tissues and reducing the opportunity of microorganisms such as bacteria and the like entering eyes. The biological material has certain biological activity and biomechanical property, can be tightly combined with the optical part, and the inherent property of the artificial cornea is still maintained, so that the best treatment and nursing effects are achieved.

The novel artificial cornea disclosed by the invention has good biocompatibility, optical performance and mechanical strength performance, and is convenient for large-scale popularization and use.

Drawings

Fig. 1(a) to (f) are schematic structural views of a biomaterial-containing posterior-penetration anterior-fixation artificial cornea according to a first embodiment of the present invention, in which fig. 1(a) is a side view of an optical column with a support base, fig. 1(b) is a top view of the optical column with the support base, fig. 1(c) is a perspective view of a fixed disk of the artificial cornea, fig. 1(d) is a perspective view of an upper ring of the artificial cornea, fig. 1(e) is a complete assembly view of an optical portion of the artificial cornea, and fig. 1(f) is a view showing effects of the artificial cornea in vivo.

Fig. 2(a) to (g) are schematic structural views of a biomaterial-containing anterior-through posterior fixated artificial cornea according to a second embodiment of the present invention, wherein fig. 2(a) is a side view of an optical lens column, fig. 2(b) is a perspective view of a front fixation disk, fig. 2(c) is a perspective view of a posterior fixation disk, fig. 2(d) is a perspective view of a locking ring, fig. 2(e) is a complete assembly view of an optical portion of the artificial cornea, fig. 2(f) is a complete assembly cross-sectional view of the artificial cornea taken along line a-a of fig. 2(e), and fig. 2(g) is an in vivo efficacy view of the artificial cornea.

Fig. 3(a) to (b) are photographs showing the state after other artificial corneas were performed, fig. 3(a) is a photograph showing the stent exposure for 3 months after the implantation of the russian artificial cornea stent (Boston type 1 artificial cornea) containing no biomaterial, and fig. 3(b) is a photograph showing the long-term in-place state of the russian artificial cornea stent (Boston type 1 artificial cornea) using the auricular cartilage reinforcement repair.

Fig. 4 is a photograph showing the respective components of the optical portion of the actual product of the back-wearing anterior immobilization artificial cornea containing the biomaterial of the present invention.

Detailed Description

The artificial cornea containing the biological material comprises an optical part and a biological material component, wherein the biological material component is made of the biological material, and the biological material comprises autologous material and/or non-autologous material.

Most of the materials used for artificial cornea stents in the past are polymethyl methacrylate (PMMA), titanium alloy and other materials. The materials respectively have the defects of poor biocompatibility, insufficient compressive strength and bending strength, complicated operation, limitation of large-scale popularization and application and the like. However, the inventor creatively adopts autologous materials and/or non-autologous materials to manufacture the artificial cornea bracket and the reinforcing materials for the first time, and the cartilage has not been used or reported in the artificial cornea bracket manufacturing process. The invention proves and effectively adopts autologous materials and/or non-autologous materials to manufacture the artificial cornea bracket and the reinforcing material for the first time.

The autologous material and/or the non-autologous material has good biocompatibility and good biological and physical properties, meets the biological and physical properties required by the artificial cornea, and has sufficient material source and proper price.

In a specific embodiment, the autologous cartilage is preferably autologous auricular cartilage, the non-autologous material is one or more of non-autologous cartilage, a tissue engineering material, a decellularized material, a composite stem cell chondrogenic bone and a polymer biomaterial, wherein the non-autologous cartilage is non-autologous auricular cartilage, the tissue engineering material is tissue engineering bone or cartilage, the decellularized material is a decellularized bone tissue or cartilage tissue, and the composite stem cells used in the composite stem cell chondrogenic bone are various source stem cells, preferably mesenchymal stem cells, embryonic stem cells or induced pluripotent stem cells. The non-autologous material is particularly preferably decellularized cartilage and composite stem cell chondrogenic,

the tissue engineering material and the decellularized material can be derived from human or animals, such as skin, pleuroperitoneal membrane, esophageal mucosa, small intestinal mucosa, pericardium, blood vessels, nerves, heart valves, bones, cartilages, tendons, amnions, placentas, and the like, and the decellularized tissue is obtained after the processes of virus inactivation, degreasing, decellularization and the like, is a three-dimensional reticular structure without cells, and reserves extracellular matrix components. Methods for preparing decellularized cells are known to those of ordinary skill in the art. Bovine, porcine or human tissue is preferred.

The tissue engineering bone or cartilage is bone or cartilage synthesized by tissue engineering, the decellularized bone tissue or cartilage tissue is bone tissue or cartilage tissue without immunogenicity or with low immunogenicity after cells are removed by a chemical or physical method, and the macromolecular biomaterial comprises cellulose, chitin, hyaluronic acid, collagen, gelatin, sodium alginate, polyurethane, silicone rubber, polyester fiber, polyvinylpyrrolidone, polyether ether ketone, polymethyl methacrylate, polyvinyl alcohol, polylactic acid, polyethylene and the like. Stem cell (in vitro or in vivo) chondrogenesis is cartilage formed by using stem cell composite biological material, wherein the stem cell is stem cell of various sources, preferably mesenchymal stem cell, embryonic stem cell or induced pluripotent stem cell.

In a particular embodiment, the optical portion penetrates a patient's cornea when implanted therein, and the biomaterial element may replace the patient's cornea or be located on an anterior surface of the patient's cornea when implanted therein.

The fixing mode of the artificial cornea can comprise two fixing modes of a back-wearing type front fixing mode and a front-wearing type back fixing mode. Back-through anterior fixation is shown in FIG. 1 with the primary fixation element (e.g., the upper ring) on the corneal surface, and anterior-through posterior fixation is shown in FIG. 2 with the primary fixation element (e.g., the clasp) inside or behind the cornea.

In a specific embodiment, the optical portion includes an optical lens column and other portions connected to the optical lens column, the other portions are made of the same material as the optical lens column, the optical portion can perform an optical function after being implanted in a patient, and the other portions can perform a function of fixing the optical lens column.

In a preferred embodiment, the other part comprises a support table and/or a fixing plate, the other part further comprises an upper ring when the front-through type front fixing is performed, and the other part further comprises a lock catch when the front-through type rear fixing is performed.

Wherein, the upper ring is internally provided with screw threads and is positioned on the outermost surface of the artificial cornea, so that the growth of surrounding tissues can be prevented, and the surface of the artificial cornea forms an artificial cornea front membrane. The upper ring may be composed of the same inorganic material as the mirror cylinder material, preferably PMMA.

The lock catch is a structure for fixing the whole artificial cornea, and the lock catch structure is fixed after entering the clamping groove of the mirror column, so that the front fixing disc and the rear fixing disc are prevented from slipping off from the mirror column. The lock catch can be made of metal such as titanium.

The optical lens column may be made of at least one material selected from the group consisting of poly (hydroxyethyl methacrylate), poly (methyl methacrylate), silicone gel, and glass, and preferably made of medical grade poly (methyl methacrylate) (PMMA).

In a specific embodiment, the other part connected with the optical lens column is a support table and/or a fixed disc, preferably, the fixed disc may be made of PMMA or a titanium alloy material, that is, the fixed disc may be a PMMA or a titanium disc.

In a specific embodiment, the optic cylinder replaces all or part of the original lamellar and/or full-thickness cornea of the patient when implanted in the cornea of the patient. Although the cornea is thin, the structure of the cornea can be divided into an epithelial layer, a front elastic layer, a stroma layer, a back elastic layer and a corneal endothelial layer from outside to inside, wherein the lamellar keratoplasty is an operation which is performed by taking partial tissues of the cornea as an operation object, only a pathological corneal superficial layer tissue is cut off, a recipient cornea with a relatively complete deep layer still remains as a transplantation bed, and then a corneal material superficial layer corneal lamella with the same size and thickness is taken to be sewn on a wound surface of the cornea of a patient.

In one embodiment, the patient's autologous cornea may be used as a carrier, or the donor cornea may be used as a carrier, which may save the donor cornea and costs, or the donor cornea may be used as a carrier in cases where the patient's cornea is severely damaged or of insufficient thickness, including glycerol preserved or other acellular xenogenic stromal corneas.

In a specific embodiment, the other portion is integrated with or connected to the optical lens column to fix the optical lens column to the eye.

In a specific embodiment, the autologous material and/or the non-autologous material is cut and shaped according to a certain cornea curvature design form by a manual or computer-assisted 3D cutting mode, and can be in a circular shape, an oval shape or various irregular shapes, can be in various thicknesses, can contain holes with different diameters, can be adhered with an optical column lens into a whole body, or can be used as a reinforcing material in front of a similar cornea/artificial cornea bracket. The autologous material and/or the non-autologous material of the invention corrects the characteristics suitable for the microenvironment of the eyes in the process of forming cartilage in vivo and in vitro, avoids the reduction and dissolution of the volume of the cartilage tissue caused by degradation, and solves the problems of long-term anterior movement and discharge of the artificial corneal scaffold in situ.

In a specific embodiment, the artificial cornea is a composite artificial cornea, and the composite artificial cornea refers to an artificial cornea containing the biological material and the organic material.

In one embodiment, the compound artificial cornea comprises an optical lens column with screw threads, a supporting platform connected with the optical lens column into a whole, a fixed disk capable of being screwed with the screw threads on the optical lens column, and an upper ring and/or a locking ring structure. The upper ring is a ring-shaped component with internal threads and is mainly used for front fixing, and the lock ring is mainly used for rear fixing, and is an embodiment of the lock catch.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

Fig. 1(a) to (f) are schematic structural views of a biomaterial-containing posterior-penetration anterior fixation artificial cornea according to a first embodiment of the present invention, fig. 1(a) is a side view of an optical column with a support base, fig. 1(b) is a top view of the optical column with the support base, fig. 1(c) is a perspective view of a fixed plate of the artificial cornea, fig. 1(d) is a perspective view of an upper ring of the artificial cornea, fig. 1(e) is a complete assembly view of an optical portion of the artificial cornea, and fig. 1(f) is a view showing effects of the artificial cornea in vivo.

In the first embodiment, as shown in fig. 1(a) and 1(b), the optical lens column in the optical portion may be an optical lens column with a larger outer diameter, such as a multi-step cylindrical structure or a cylindrical structure with threads on the outer surface, which is located inside or between layers of the patient's cornea when the optical lens column is implanted in the patient's cornea, the support table for supporting the artificial cornea may be integrally connected to the optical lens column, and the optical lens column may be made of any material selected from the group consisting of Polyhydroxyethylmethacrylate (PHEMA), polymethyl methacrylate (PMMA), silicone gel, and glass, and preferably made of a medical grade polymethyl methacrylate material.

Fig. 1(c) is a perspective view of a fixed disk of an artificial cornea, which can be a PMMA or titanium disk, and the fixed disk can be a continuous ring structure with holes, wherein the number of the holes is not limited, and the holes can be also not provided, and the diameter and distribution are not limited. Three evenly distributed annular closed loop structures and two evenly distributed annular closed loop structures. The artificial cornea is used for being implanted between corneal layers in an operation, the design of two loops or a plurality of loops can be adopted according to corneal conditions, the radian of the artificial cornea is equivalent to that of the cornea, the center of the artificial cornea is in a platform shape, compared with the traditional artificial cornea, the artificial cornea can reduce the separation area between the corneal layers to the maximum extent, the strength of corneal tissues is kept, the stability of the artificial cornea is improved, the repair and the reset of anterior tissues of the artificial cornea are facilitated, and the operations of suture fixation and the like by using sutures are facilitated.

FIG. 1(d) is a perspective view of the upper ring of the artificial cornea, which is a component for fixing the artificial cornea for the back-wearing type anterior fixation, and the upper ring can be internally threaded and screwed with the optical lens column, and is located on the outermost surface of the cornea to prevent the surrounding tissues from growing in, and the artificial cornea surface forms the artificial cornea anterior membrane.

FIG. 1(e) is a complete assembly of the optical portion of the artificial cornea, seen from the outer surface of the cornea to the interior, with the upper ring, the fixed disk and the support platform in that order on the optic cylinder.

FIG. 1(f) is a diagram showing the effect of the artificial cornea in vivo. As shown in fig. 1(f), the optical portion penetrates the patient's cornea when implanted therein, and the biomaterial member is located on the outer surface of the patient's cornea when implanted therein. Specifically, the support platform is located on the posterior side of the cornea, and the fixed disk is located on the anterior side of the cornea, where the posterior side may also be referred to as the inner side, i.e., the intracorporeal side, and the anterior side may also be referred to as the outer side, i.e., the extracorporeal side. And the biomaterial element is located more anterior to the cornea than the fixed disk, with the upper ring located most anterior to the cornea and on the outer surface of the conjunctiva or skin.

The biomaterial component has circular, elliptical or various irregular shapes in plan view, can have various thicknesses, can contain holes with different diameters, can be integrally bonded with an optical cylinder, or can be used as a reinforcing material in front of a cornea/artificial cornea-like support. The biomaterial component is composed of the above-mentioned biomaterial, which includes autologous material and/or non-autologous material. The autologous material is autologous cartilage, the autologous cartilage can be autologous auricular cartilage, the non-autologous material is one or more of non-autologous cartilage, a tissue engineering material, a decellularized material, composite stem cell chondroblast and a high molecular biological material, wherein the non-autologous cartilage is non-autologous auricular cartilage, the tissue engineering material is tissue engineering bone or cartilage, the decellularized material is decellularized bone tissue or cartilage tissue, the composite stem cells used in the composite stem cell chondroblast are various source stem cells and can be mesenchymal stem cells, embryonic stem cells or induced pluripotent stem cells. Here, the Tensor vesicle in the figure refers to subconjunctival tissue.

Fig. 2(a) to (g) are schematic structural views of a biomaterial-containing anterior-through posterior fixated artificial cornea according to a second embodiment of the present invention, in which fig. 2(a) is a side view of an optical lens column, fig. 2(b) is a perspective view of a front fixation disk, fig. 2(c) is a perspective view of a posterior fixation disk, fig. 2(d) is a perspective view of a locking ring, fig. 2(e) is a complete assembly view of an optical portion of the artificial cornea, fig. 2(f) is a complete assembly cross-sectional view of the artificial cornea taken along line a-a of fig. 2(e), and fig. 2(g) is an in vivo efficacy view of the artificial cornea.

The artificial cornea according to the second embodiment of the present invention is a front-through type posterior fixation artificial cornea, and the optical column thereof is a cylindrical structure with a thread on the outer surface, without a support table, as shown in fig. 2 (a). The front-through type posterior fixation artificial cornea may have a front fixation disk and a posterior fixation disk, wherein fig. 2(b) is a perspective view of the front fixation disk and fig. 2(c) is a perspective view of the posterior fixation disk, and the composition and structure of the front fixation disk and the posterior fixation disk may be the same as those of the fixation disk of the first embodiment of the present invention. The rear fixed disk and the front fixed disk may not have the same size and thickness, for example, the rear fixed disk may have a diameter smaller than that of the front fixed disk, and the rear fixed disk may have a thickness greater than that of the front fixed disk.

Fig. 2(d) is a perspective view of the locking ring. The locking ring structure enters the clamping groove of the mirror column and then is fixed, so that the structure of the rear fixing disc is prevented from slipping off the mirror column. The lock catch can be made of metal such as titanium.

Fig. 2(e) is a complete assembly view of the optical portion of the artificial cornea, and fig. 2(f) is a cross-sectional view taken along line a-a of fig. 2(e), from which fig. 2(f) it can be seen that the upper ring, the front fixing disk, the rear fixing disk and the locking ring are sequentially provided on the optic cylinder, from the outside surface of the cornea toward the inside, i.e., from the top to the bottom in the direction of the drawing.

The artificial cornea can be assembled by adopting a design that the back fixing disc and the lock catch are integrated, for example, a C-shaped design is made on the back fixing disc, and the lock catch is put on the back fixing disc.

FIG. 2(g) is a diagram of an in vivo implementation of an artificial cornea, with an optical portion penetrating a patient's cornea when implanted therein, and a biomaterial element on an outer surface of the patient's cornea when implanted therein. The optical part comprises an optical lens column and other parts connected with the optical lens column, the other parts can be various fixing structures described above, and are positioned on the inner side and the outer side of the patient cornea/donor cornea and/or autologous/allogeneic biomaterials when the optical lens column is implanted into the patient cornea, so that the optical lens column can be firmly fixed, the artificial cornea can be prevented from falling off when the intraocular pressure of the patient is increased, the gap between the optical part and the surrounding tissues is reduced, and the opportunity of microorganisms such as bacteria and the like to enter the eye is further reduced. The other part is made of the same material as the optical lens column or other biological shape-compatible materials, and the optical part can play an optical role and/or fix the optical lens column after being implanted in the body of a patient. The optical lens column can replace all or part of the original lamellar and/or full-thickness cornea of a patient when being implanted into the cornea of the patient. The other parts are integrated with or connected with the optical lens column to play a role in fixing the optical lens column on the eye.

Fig. 3(a) to (b) are photographs showing the state after the implementation of another artificial cornea, fig. 3(a) is a photograph showing the exposure of a stent of russian artificial cornea (Boston type 1 artificial cornea) without a biomaterial for 3 months after the implantation of the stent, and fig. 3(b) is a photograph showing the good surface growth and long-term in-place of the russian artificial cornea stent (Boston type 1 artificial cornea) using the auricular cartilage reinforcement repair, in which the russian artificial cornea itself does not contain a biomaterial. As shown in fig. 3(a), the artificial corneal scaffold containing no biomaterial has a problem of exposure (corneal lysis). And the reinforcement and repair of the Russian artificial cornea scaffold after exposure (corneal lysis) was performed by using the auricular cartilage, as shown in FIG. 3(b), the in-situ performance was improved to some extent. However, the structure of the artificial cornea of Boston 1 for auricular cartilage reinforcement of FIG. 3(b) is completely different from that of the artificial cornea of the present invention in that it is composed of a metallic titanium loop structure implanted between the corneal layers, and the operation is completed in two stages, whereas the operation of the artificial cornea having the structure of the artificial cornea of the present invention, particularly the optical portion structure, can be completed in one stage, overcoming the disadvantages of the artificial cornea of Boston 1 type and having excellent positioning property.

Fig. 4 is a photograph showing the respective components of the optical portion of the actual product of the back-wearing anterior immobilization artificial cornea containing the biomaterial of the present invention. The components shown from left to right in the figure are respectively an optical lens column which is connected with a support platform and is provided with screw threads, an upper ring structure and a fixed disk which can be screwed with the screw threads on the optical lens column, wherein the support platform and the optical lens column are connected into a whole. Wherein the fixed disk is a continuous ring structure with holes, wherein the biological material can be arranged on the fixed disk.

Examples

The invention adopts the exposure rate of the artificial cornea bracket to evaluate the implementation effect of the artificial cornea, and the exposure rate is also the rejection rate. According to the experience of the applicant with MICOF and Boston type II keratoprostheses, patients with existing keratoprostheses composed of PMMA implanted without biomaterial members had an exposure (rejection) of 60% 5 years after surgery. In contrast, the applicant performed a total of 156 implantation surgeries of artificial corneas containing autologous auricular cartilage, and as a result, only 6 cases were exposed after 5 years, and the exposure rate was decreased to 3.8%.

While the preferred embodiments of the present invention have been described above, the present invention is not limited to these embodiments, and various modifications can be made without departing from the scope of the present invention.

Industrial applicability

The artificial cornea containing the biological material can enhance the biological integration of the artificial cornea and reduce the infection incidence rate of the artificial cornea in the using process, and the artificial cornea has good biocompatibility and mechanical strength performance, so the artificial cornea is convenient for large-scale popularization and use.

Claims

1. A keratoprosthesis comprising a biological material, wherein:

the artificial cornea comprises an optical part and a biomaterial component, the biomaterial component is made of biomaterial, the biomaterial comprises autologous material and/or non-autologous material, the optical part penetrates the patient's cornea when being implanted into the patient's cornea, the biomaterial component is cut and shaped according to the cornea curvature design form, the biomaterial component replaces the patient's cornea or is positioned on the front surface of the patient's cornea when being implanted into the patient's cornea and is used as a reinforcing material, the artificial cornea is fixed in a fixing mode of front-wearing type front fixing or front-wearing type back fixing,

the optical part comprises an optical lens column and other parts connected with the optical lens column, the materials of the other parts are the same as or different from the materials of the optical lens column, the optical part can play an optical role after being implanted into a patient body, and the other parts play a role in fixing the optical lens column,

the other parts comprise a support table and/or a fixed disc, when the support table and/or the fixed disc are fixed in the front of the back-wearing type, the other parts further comprise an upper ring, and when the support table and/or the fixed disc are fixed in the back-wearing type, the other parts further comprise a lock catch.

2. The artificial cornea of claim 1, wherein:

the autologous material is autologous cartilage, and the non-autologous material is any one or more of non-autologous cartilage, a tissue engineering material, a decellularized material, stem cell chondrogenic cartilage and a high molecular biological material.

3. A keratoprosthesis as claimed in claim 2, wherein:

the autologous cartilage is autologous auricular cartilage.

4. A keratoprosthesis as claimed in claim 3, wherein:

the non-autologous cartilage is non-autologous auricular cartilage, the tissue engineering material is tissue engineering bone or cartilage, the decellularized material is decellularized bone tissue or cartilage tissue, and stem cells used in stem cell chondrogenesis are stem cells from various sources.

5. A keratoprosthesis as claimed in claim 2, wherein:

the stem cell chondrogenic cells are mesenchymal stem cells, embryonic stem cells or induced pluripotent stem cells.

6. An artificial cornea according to any one of claims 1 to 5, wherein:

the optical lens column is made of at least one material selected from the group consisting of poly (hydroxyethyl methacrylate), poly (methyl methacrylate), silicone gel and glass.

7. An artificial cornea according to any one of claims 1 to 5, wherein:

the optical lens column is made of medical grade polymethyl methacrylate (PMMA) material.

8. An artificial cornea according to any one of claims 1 to 5, wherein:

the optical lens column replaces all or part of the original lamellar and/or full-thickness cornea of a patient when being implanted into the cornea of the patient.

9. An artificial cornea according to any one of claims 1 to 5, wherein:

the other parts are structures which are integrated with or connected with the optical lens column and play a role in fixing the optical lens column on the eye.

10. An artificial cornea according to any one of claims 1 to 5, wherein:

the artificial cornea is a composite artificial cornea.

11. A keratoprosthesis as claimed in claim 10, wherein:

the combined artificial cornea comprises an optical lens column with threads, a supporting table connected with the optical lens column into a whole, and a fixed disc capable of being in threaded connection with the threads on the optical lens column, and comprises an upper ring and/or a lock ring.

12. Use of a biomaterial for the preparation of a replacement patient's cornea or a reinforcing material located on the anterior surface of the patient's cornea for an implant for the treatment of corneal blindness, wherein the implant is a keratoprosthesis according to any one of claims 1 to 11.