A composite keratoprosthesis and a method of making the same

Abstract

The application discloses a composite artificial cornea and a preparation method thereof. The composite artificial cornea comprises a mirror column and a biological skirt. An annular gap is arranged on the inner side edge of the biological skirt. The outer side edge of the mirror column is embedded into the inside of the biological skirt along the gap, and the outer side edge of the mirror column is fixed in the gap through casting liquid. The application has the beneficial effects that: by arranging the annular gap on the inner side edge of the biological skirt, then embedding the outer side edge of the mirror column into the inside of the biological skirt along the gap, a interference fit structure is formed, preliminary fixation is formed between the mirror column and the gap, and the outer side edge of the mirror column is fixed in the gap through the casting liquid, so that the casting liquid can permeate and fill the gap, the mirror column and the biological skirt are connected into an integrated whole, secondary fixation is formed, the connection strength of the composite artificial cornea is improved, and the risk of the mirror column falling off is reduced.

Description

Technical Field

[0001] This invention relates to the field of artificial cornea technology, and in particular to a composite artificial cornea and its preparation method. Background Technology

[0002] Corneal blindness is the second leading cause of blindness. According to WHO statistics, there are approximately 60 million people with corneal blindness worldwide, and about 5 million in my country. This does not include the approximately 10-15 million people with corneal-related low vision (≤0.1). my country sees 100,000 new cases of corneal blindness annually, with 70% occurring in young adults and 15% in children. All these patients can regain their sight through corneal transplantation. Currently, due to a shortage of donated corneas, over 90% of patients do not receive timely and effective treatment. Artificial corneas are an effective way to address this shortage.

[0003] There are currently two types of artificial corneas: bio-corneas and artificial corneas. Both have their own shortcomings, but their advantages can make up for the shortcomings of the other: ① Bio-corneas: have good tissue compatibility and can heal with tissues, but postoperative vision is not ideal and they are only suitable for lamellar keratoplasty; ② Artificial corneas: can achieve good postoperative vision, but cannot heal with tissues, have more complications, and have a three-year extrusion rate of 42% to 82%.

[0004] In view of this, CN109157305A discloses a composite artificial cornea and its preparation method, including a central optical column made of poly(hydroxyethyl methacrylate) (PHEMA), a corneal skirt structure made of decellularized matrix hydrogel, and an intermediate interlayer mesh scaffold connecting the central optical column and the corneal skirt structure, integrating the advantages of existing biological corneas and artificial corneas. However, the "lens-scaffold-skirt" structure of the above-mentioned composite artificial cornea is connected by the intermediate interlayer mesh scaffold, resulting in insufficiently firm connection between the lens column and the skirt, posing a risk of lens column detachment. Summary of the Invention

[0005] To address the aforementioned problems, this invention proposes a composite artificial cornea and its preparation method, primarily resolving the issues raised in the background technology.

[0006] To solve the above-mentioned technical problems, the first aspect of the present invention provides a composite artificial cornea, including a lens column and a bio-skirt, wherein the inner edge of the bio-skirt is provided with an annular slit, the outer edge of the lens column is embedded in the interior of the bio-skirt along the slit, and the outer edge of the lens column is fixed in the slit by casting liquid.

[0007] In some embodiments, an enlarged annular connector is provided on the outer edge of the mirror pillar, and the annular connector is integrally formed with the mirror pillar.

[0008] In some embodiments, the surface of the annular connector is provided with a through hole perpendicularly.

[0009] In some embodiments, the outer edge of the mirror pillar is uniformly provided with a plurality of radially extending cable connectors along its own circumference, the ends of the cable connectors forming enlarged portions, and the cable connectors, the enlarged portions, and the mirror pillar are integrally formed.

[0010] In some embodiments, the surface of the enlarged portion is provided with a through hole perpendicularly.

[0011] In some embodiments, the biological skirt is defined as a transition zone and a peripheral zone from the inner edge to the outer edge, respectively. The fissure is located on the inner edge of the transition zone. The transition zone is also provided with a porous structure connected to the fissure. The biological skirt is uniformly provided with a plurality of radial tunnel structures along its own circumference. Each tunnel structure penetrates the transition zone and the peripheral zone.

[0012] In some embodiments, the porous structure is formed by expansion.

[0013] In some embodiments, the mirror column is made of silicone hydrogel or hydrated polymer.

[0014] In some embodiments, the bio-skirt is made of natural biomaterials or of an equivalent extracellular matrix synthesized in vitro from artificial biomaterials.

[0015] A second aspect of the present invention provides a method for preparing a composite artificial cornea, comprising the following steps:

[0016] Using silicone hydrogel or hydrated polymer as materials, a mirror column with the desired refractive power is prepared by micro-turning or casting. The outer edge of the mirror column is provided with an integrally formed annular connector or a strip connector.

[0017] An equivalent extracellular matrix synthesized in vitro from natural decellularized biomaterials or artificial biomaterials is used to prepare a biological skirt using methods such as direct fiber writing, electrospinning, 3D printing, or molecular interpenetrating network method. The biological skirt is defined as a transition zone and a peripheral zone from the inner edge to the outer edge, respectively. A triangular excision is performed on the inner edge of the transition zone to form a slit. The transition zone is then expanded using an expansion method to form a porous structure. Several radial tunnel structures are formed by intermittently penetrating the transition zone and the peripheral zone along the circumference of the biological skirt.

[0018] The mirror column is placed in the central hole of the biological skirt, and the annular connector or the strip connector is embedded in the fissure. Casting liquid is injected between the outer edge of the mirror column and the biological skirt using a casting molding method combined with in-situ polymerization until the casting liquid penetrates and fills the porous structure and all of the tunnel structure, polymerizing to form a locally interpenetrating network.

[0019] The beneficial effects of this invention are as follows: by setting an annular slit on the inner edge of the bio-skirt, and then embedding the outer edge of the lens pillar into the interior of the bio-skirt along the slit, an interference fit structure is formed, and a preliminary fixation is formed between the lens pillar and the slit. The outer edge of the lens pillar is fixed in the slit by casting liquid, which allows the casting liquid to penetrate and fill the slit, connecting the lens pillar and the bio-skirt into one, forming a secondary fixation, improving the connection strength of the composite artificial cornea and reducing the risk of lens pillar detachment. Attached Figure Description

[0020] Figure 1 This is a schematic diagram of the composite artificial cornea disclosed in Embodiment 1 of the present invention;

[0021] Figure 2 This is a schematic diagram of the structure of one of the connectors disclosed in Embodiment 1 of the present invention;

[0022] Figure 3 This is a schematic diagram of the structure of another connector disclosed in Embodiment 1 of the present invention;

[0023] Figure 4 for Figure 1 A magnified view of a portion of the area along line A. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of this invention clearer and more explicit, the content of this invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and not intended to limit it. Furthermore, it should be noted that, for ease of description, only the parts relevant to this invention are shown in the accompanying drawings, not all of them.

[0025] Example 1

[0026] This embodiment proposes a composite artificial cornea, such as Figure 1 As shown, it includes a mirror column 1 and a biological skirt 2. The inner edge of the biological skirt 2 is provided with an annular slit 201. The outer edge of the mirror column 1 is embedded in the interior of the biological skirt 2 along the slit 3, and the outer edge of the mirror column 1 is fixed in the slit 3 by casting liquid.

[0027] In this embodiment, an annular slit 201 is provided on the inner edge of the bio-skirt 2, and then the outer edge of the lens post 1 is embedded into the interior of the bio-skirt 2 along the slit 3 to form an interference fit structure. The lens post 1 and the slit 3 are initially fixed together, and the outer edge of the lens post 1 is fixed in the slit 3 by casting liquid. This allows the casting liquid to penetrate and fill the slit 3, connecting the lens post 1 and the bio-skirt 2 into one, forming a secondary fixation, improving the connection strength of the composite artificial cornea and reducing the risk of lens post 1 falling off.

[0028] To further enhance the connection strength between the mirror column 1 and the biological skirt 2, preferably, a connector is provided on the outer edge of the mirror column 1. Two alternative embodiments are provided below.

[0029] In one of the alternative implementation schemes, such as Figure 2 As shown, an enlarged annular connector 101 is provided on the outer edge of the mirror column 1. The annular connector 101 is integrally formed with the mirror column 1. In this design, the enlarged annular connector 101 can slightly open the crack 3, bringing a certain frictional force and making it less likely for the mirror column 1 to fall off the biological skirt 2. Furthermore, the surface of the annular connector 101 is vertically provided with through holes 102. During the infiltration process, the casting liquid not only fills the crack 3 but also fills the through holes 102, forming a complex interpenetrating network structure, which further enhances the connection between the "mirror-skirt" structure.

[0030] In one of the alternative implementation schemes, such as Figure 3 As shown, the outer edge of the mirror column 1 is uniformly provided with a plurality of radially extending cable connectors 201 along its circumference. The ends of the cable connectors 201 form enlarged portions 202. The cable connectors 201, enlarged portions 202, and mirror column 1 are integrally formed. In this design, the radially extending cable connectors 201 can penetrate deep into the fissures 3, while the enlarged portions 202 can slightly open the fissures 3, bringing a certain frictional force and making it less likely for the mirror column 1 to fall off the biological skirt 2. Furthermore, the surface of the enlarged portions 202 is vertically provided with through holes 203. Similarly, during the infiltration process, the casting liquid not only fills the fissures 3 but also fills the through holes 203, forming a complex interpenetrating network structure, further enhancing the connection between the "mirror-skirt" structure.

[0031] Better, such as Figure 4 As shown, the biological skirt 2 is defined as a transition zone 21 and a peripheral zone 22 from its inner edge to its outer edge. The fissure 3 is located on the inner edge of the transition zone 21. The transition zone 21 also has a porous structure 4 connected to the fissure 3. The biological skirt 2 has several radially arranged tunnel structures 5 evenly distributed along its circumference, each tunnel structure 5 penetrating both the transition zone 21 and the peripheral zone 22. It should be noted that both the transition zone 21 and the peripheral zone 22 are annular areas.

[0032] In the above scheme, the casting liquid permeates and fills the porous structure 4 in the transition zone 21 and the radial tunnel structure 5 that runs through the entire skirt, connecting the "mirror-skirt" as a whole. In some schemes, the casting liquid can also permeate and fill the aforementioned through holes 102 or 203, resulting in the casting liquid permeating and filling the porous structure 4, tunnel structure 5, and through holes, forming a complex intersecting network structure, further enhancing the connection between the "mirror-skirt" structures.

[0033] The porous structure 4 is formed by expansion. Specifically, the peripheral area 22 of the biological skirt 2 is compressed, and the uncompressed transition area 21 is expanded by low-temperature high-pressure expansion method to form a porous structure 4.

[0034] The mirror column 1 is made of silicone hydrogel or hydrated polymer. Among them, the hydrated polymer is selected from, but is not limited to, polyhydroxyethyl methacrylate (PHEMA), polyhydroxyethyl methacrylate, acrylate, polymethyl methacrylate (PMMA), glyceryl methacrylate, etc.

[0035] The bio-skirt 2 uses natural biomaterials or an equivalent extracellular matrix synthesized in vitro from artificial biomaterials. The natural biomaterial is decellularized corneal stroma, while the equivalent extracellular matrix is ​​synthesized in vitro from artificial biomaterials such as collagen.

[0036] Example 2

[0037] This embodiment proposes a method for preparing a composite artificial cornea, including the following steps:

[0038] Step 1: Using silicone hydrogel or hydrated polymer as material, a mirror column 1 with the expected refractive power is prepared by micro-turning or casting. An integrally formed annular connector 101 or a strip connector 201 is provided on the outer edge of the mirror column 1.

[0039] In step one, taking HAMA monomer as an example, a combination of casting and in-situ polymerization is used to fabricate the lens pillar 1. The HAMA monomer is cast into a mold with different curvatures to create PHAMA lens pillars with different refractive powers. The outer edge of the lens pillar 1 extends outwards to form an enlarged annular connector 101. The annular connector 101 is circumferentially perforated to form vertical through holes 102. Both the front and rear surfaces of the lens pillar 1 are treated with hydrophobic coating.

[0040] Step 2: Using natural decellularized biomaterials or artificial biomaterials to synthesize an equivalent extracellular matrix in vitro, a biological skirt 2 is prepared by fiber direct writing, electrospinning, 3D printing, or molecular interpenetrating network method. The biological skirt 2 is defined as the transition region 21 and the peripheral region 22 from the inner edge to the outer edge, respectively. A triangular excision is performed on the inner edge of the transition region 21 to form a slit 3. The transition region 21 is expanded by the expansion method to form a porous structure 4. Several radial tunnel structures 5 are formed by intermittently penetrating the transition region 21 and the peripheral region 22 along the circumference of the biological skirt 2.

[0041] In step two, taking decellularized corneal stroma as an example, a decellularized biological corneal stroma skirt is made using decellularization technology. The central part of the decellularized biological corneal stroma skirt is removed by trephine cutting to obtain biological skirt 2. Triangular excision is performed along the inner ring side edge of biological skirt 2, with the apex of the triangle facing the outer edge of biological skirt 2. From the apex of the triangle to the outer outer edge of biological skirt 2, 3 to 16 radial tunnel structures 5 are made parallel to the skirt surface. Finally, the peripheral area 22 of biological skirt 2 is compressed, and the uncompressed transition area 21 is expanded using a low-temperature high-pressure expansion method to form a porous structure 4.

[0042] Step 3: Place the mirror column 1 in the central hole of the biological skirt 2, and embed the annular connector 101 or the strip connector 201 into the fissure. Use the casting molding method combined with the in-situ polymerization method to inject casting liquid between the outer edge of the mirror column 1 and the biological skirt 2 until the casting liquid penetrates and fills the porous structure 4 and all the tunnel structures 5, and polymerizes to form a local interpenetrating network.

[0043] In step three, the prefabricated lens column 1 and bio-skirt 2 are placed in the mold, and HAMA monomer is cast. The casting liquid fills the gap between the annular connector 101 and the slit 3, the through hole 102 on the annular connector 101, the porous structure 4 in the bio-skirt 2, and all the tunnel structures 5. After the HAMA monomer is polymerized in situ to form PHAMA, a local cross-penetrating network is formed, connecting the "lens-skirt" into one, and the resulting composite artificial corneal structure has high strength.

[0044] The above embodiments are merely illustrative of the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be construed as limiting the scope of protection of the present invention. All equivalent changes or modifications made based on the essence of the content of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A composite artificial cornea, comprising a lens column and a biological skirt, characterized in that, The inner edge of the biological skirt is provided with an annular slit, and the outer edge of the mirror column is embedded in the interior of the biological skirt along the slit, and the outer edge of the mirror column is fixed in the slit by casting liquid. The outer edge of the mirror pillar is uniformly provided with a plurality of radially extending strip connectors along its own circumference. The ends of the strip connectors form enlarged portions. The strip connectors, the enlarged portions and the mirror pillar are integrally formed. The radially extending strip connectors can penetrate into the cracks, and the enlarged portions can slightly open the cracks. A through hole is vertically provided on the surface of the enlarged part; The biological skirt is defined as a transition zone and a peripheral zone from the inner edge to the outer edge, respectively. The fissure is located on the inner edge of the transition zone. The transition zone is also provided with a porous structure connected to the fissure. The biological skirt is uniformly provided with a number of radial tunnel structures along its own circumference. Each tunnel structure penetrates the transition zone and the peripheral zone. The porous structure is formed by expansion, and the casting liquid permeates and fills the porous structure, tunnel structure and through holes, and aggregates to form a locally interpenetrating network.

2. The composite artificial cornea as described in claim 1, characterized in that, The mirror column is made of silicone hydrogel.

3. The composite artificial cornea as described in claim 1, characterized in that, The mirror column is made of a hydrated polymer.

4. The composite artificial cornea as described in claim 1, characterized in that, The biological skirt is made of natural biological materials or an equivalent extracellular matrix synthesized in vitro from artificial biological materials.

5. A method for preparing a composite artificial cornea, characterized in that, Includes the following steps: Using hydrated polymers as materials, a lens column with the desired refractive power is prepared by micro-turning or casting. The outer edge of the lens column is uniformly provided with a plurality of radially extending strip connectors along its own circumference. The ends of the strip connectors form enlarged portions. The strip connectors, the enlarged portions, and the lens column are integrally formed. An equivalent extracellular matrix synthesized in vitro from natural decellularized biomaterials or artificial biomaterials is used to prepare a biological skirt via electrospinning, 3D printing, or molecular interpenetrating network method. The biological skirt is defined as a transition zone and a peripheral zone from the inner edge to the outer edge, respectively. A triangular excision is performed on the inner edge of the transition zone to form a slit. The transition zone is then expanded using an expansion method to form a porous structure. Several radial tunnel structures are formed by intermittently penetrating the transition zone and the peripheral zone along the circumference of the biological skirt. The mirror column is placed in the central hole of the biological skirt, and the cable connector is embedded in the fissure. The enlarged part can slightly open the fissure. Casting liquid is injected between the outer edge of the mirror column and the biological skirt using a casting molding method combined with in-situ polymerization until the casting liquid penetrates and fills the porous structure, all the tunnel structure and the through hole, and polymerizes to form a locally interpenetrating network.

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