CN113101010A - Artificial cornea in corneal stroma and preparation method thereof - Google Patents
Artificial cornea in corneal stroma and preparation method thereof Download PDFInfo
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- CN113101010A CN113101010A CN202110397721.0A CN202110397721A CN113101010A CN 113101010 A CN113101010 A CN 113101010A CN 202110397721 A CN202110397721 A CN 202110397721A CN 113101010 A CN113101010 A CN 113101010A
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
- A61F2/142—Cornea, e.g. artificial corneae, keratoprostheses or corneal implants for repair of defective corneal tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
- A61F2/148—Implantation instruments specially adapted therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
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- Health & Medical Sciences (AREA)
- Transplantation (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Prostheses (AREA)
Abstract
The invention discloses an artificial cornea in a corneal stroma and a preparation method thereof. The preparation method comprises the following steps: preparing a dry silicon hydrogel mould blank: polymerizing a silicon hydrogel monomer into a dry-state silicon hydrogel mould blank; turning and forming: fixing the dry-state silicon hydrogel model blank on a numerical control lathe, and sequentially turning a front plate and a light column part of the artificial cornea, wherein the curvature radius of the front plate is consistent with that of the front surface of the cornea, the central area of the front plate is thick, and the peripheral part of the front plate is gradually thinned; polishing and hydrating: and polishing the front surface of the artificial cornea front plate and the back surface of the optical column part, and fully hydrating and softening to form the colloidal artificial cornea. The artificial cornea of the invention is implanted between the corneal tissue layers of patients, and a layer of autologous or allogeneic lamellar corneal tissue covers the surface of the artificial cornea, so that the surface of the patient cornea after the operation has no junction between the artificial cornea and the patient cornea, and the leakage and the artificial cornea falling off after the operation are avoided.
Description
Technical Field
The invention relates to the technical field of medical materials, in particular to an artificial cornea in a corneal stroma and a preparation method thereof.
Background
The cornea is a transparent film at the most anterior part of the eyeball, and the average thickness of the center is 520 microns and 540 microns, so that the cornea can protect the eyeball and provide most of the refractive power for the eyeball. Because the cornea is directly contacted with the external environment, the cornea is very easy to be infected by mechanical trauma, thermal burn, chemical burn and pathogenic microorganisms, and the cornea can also have congenital hereditary or developmental abnormality, so that the cornea is diseased, and the transparent cornea becomes turbid to cause blindness of a patient. According to WHO statistics, nearly 6000 million patients are caused by corneal diseases worldwide at present, nearly 500 million patients exist in China, most patients can be cured through corneal transplantation, but most patients cannot be recovered due to the fact that cornea donation is extremely deficient, and therefore the patients cannot be subjected to corneal transplantation operation.
In recent 20 years, the emergence of artificial corneas made of high molecular materials (such as polymethyl methacrylate (PMMA)) as main raw materials and the progress of artificial cornea implantation surgery have brought new hopes for the recovery of the blindness of keratopathy. Hitherto, the artificial cornea mainly includes boston's artificial cornea (usa), AlphaCor's artificial cornea (australia), mich's artificial cornea (russia), Osteo-Odonto's artificial cornea (italy), and the like, among which boston's artificial cornea is the most effective and widely used. Although the boston keratoprosthesis is the most highly evaluated type of keratoprosthesis at present, it requires a sheet of a donor cornea with good cell viability, which can be used for penetrating corneal transplants, as a component to implant into a patient. Since the donated human cornea itself is extremely deficient, this deficiency severely limits the use of boston's artificial cornea.
Moreover, all the existing artificial corneas are difficult to overcome a crucial defect, namely, the artificial cornea material has poor histocompatibility and can not be healed with the corneal tissue of a patient after transplantation, so that the leakage of an operative wound, the artificial cornea prolapse and infection at the later stage of the operation are caused.
Therefore, the key to ensure satisfactory curative effect in the later stage of artificial cornea implantation is to avoid wound leakage and artificial cornea prolapse between the artificial cornea and the patient's cornea.
Disclosure of Invention
Aiming at the technical defects of the existing artificial cornea, the invention aims to provide the artificial cornea in the corneal stroma and the preparation method thereof, which solve the problems of wound leakage and artificial cornea prolapse after the artificial cornea is implanted, and the implantation of the artificial cornea does not need a donor cornea or only needs the donor cornea with poor cell activity.
In order to solve the technical problems, the invention adopts the following technical scheme:
the invention provides a preparation method of an artificial cornea in a corneal stroma, which comprises the following steps:
(1) preparing a dry silicon hydrogel mould blank: polymerizing a silicon hydrogel monomer into a dry-state silicon hydrogel mould blank;
(2) turning and forming: fixing the dry-state silicon hydrogel model blank on a numerical control lathe, and sequentially turning a front plate and a light column part of the artificial cornea, wherein the curvature radius of the front plate is consistent with that of the front surface of the cornea, the central area of the front plate is thick, and the peripheral part of the front plate is gradually thinned;
(3) polishing and hydrating: and (3) polishing the front surface of the artificial cornea front plate and the back surface of the optical column part prepared in the step (2), and fully hydrating and softening to form the colloidal artificial cornea.
In the step (2), the central thickness of the artificial cornea anterior plate is 70-100 microns, the peripheral part of the artificial cornea anterior plate is gradually thinned, and the diameter of the artificial cornea anterior plate is 5-8 mm.
In the step (2), the artificial cornea light pillar part has the diameter of 3-6mm and the length of 4-6 mm.
In step (2), the artificial cornea may be produced by a method such as rotational molding or cast molding.
In step (1), the mold blank material may also be silica gel, hydrogel, or polymethyl methacrylate (PMMA).
In the step (1), the preparation method of the dry-state silicon hydrogel mould blank comprises the following specific steps:
s1, weighing the following raw materials in percentage by mass: 23-40% of silicon-containing monomer, 36-52% of hydrophilic monomer, 0.05-8% of cross-linking agent, 0.05-5% of light/heat initiator and the balance of solvent;
s2, mixing and stirring the components uniformly according to the formula amount, injecting the mixture into a mold, and carrying out polymerization reaction under the conventional heating or ultraviolet lamp irradiation condition;
s3, placing the mold in an alcohol solvent with the volume fraction of 10-30% for separation, and collecting to obtain a silicon hydrogel mold blank;
s4, modifying the mold blank in isopropanol with the volume fraction of 10-20% for 1 h; the isopropanol is used as a cleaning degreaser, so that the grease material on the mould blank can be completely cleaned, the transparency of the mould blank is improved, and meanwhile, the channel on the mould blank is opened, so that the oxygen permeability coefficient of the mould blank is improved;
s5, soaking the modified mould blank with pure water for 1-3 times, then placing the mould blank in 0.9% physiological saline for 30-60 minutes, finally sealing the mould blank in a penicillin bottle with 0.9% physiological saline, and sterilizing to obtain a finished mould blank.
The silicon-containing monomer is methacryloxypropyltris (trimethylsiloxy) silane, (3-methacryloxy-2-hydroxypropoxy) propylbis (trimethylsiloxy) methylsilane, 1, 3-bis (3-methacryloxypropyl) tetrakis (trimethylsiloxy) disiloxane, poly (dimethylsiloxane) terminated bis (hydroxyalkyl), or a combination thereof.
The hydrophilic monomer is an alkyl (meth) acrylamide, N-ethyl (meth) acrylamide, N-vinylpyrrolidone, N-diethyl (meth) acrylamide, N-propyl (meth) acrylamide, N-2-hydroxyethyl (meth) acrylamide, and combinations thereof.
The solvent is 1, 2-propylene glycol, n-butanol or n-hexanol.
In the step (3), hydration and softening of the artificial cornea are carried out in physiological saline.
An artificial cornea prepared by the preparation method of the artificial cornea in the corneal stroma.
The invention has the beneficial effects that:
1. the artificial cornea is implanted between the corneal tissue layers of a patient, a layer of autologous or allogeneic lamellar corneal tissue is covered on the surface of the artificial cornea, and the surface of the patient's cornea after an operation is not intersected with the patient's cornea, so that the leakage and the artificial cornea falling off after the operation are avoided. Unlike Boston's keratoprosthesis, which requires the use of a donor cornea with good cellular viability that can be used for penetrating corneal transplantation, the keratoprosthesis of the present invention does not require the use of a donor cornea, or requires the use of lamellar corneal tissue that has poor cellular viability and cannot be used for penetrating corneal transplantation, and such a donor cornea with poor cellular viability is not deficient.
2. The artificial cornea is implanted in the corneal stroma, the surface of the artificial cornea is covered by autologous lamellar cornea or donated lamellar cornea with poor cell activity, and no interface between the artificial cornea and the patient cornea exists on the surface of the patient cornea after operation.
3. The artificial cornea prepared by the invention has the advantages of simple structure, convenient material taking and lower cost, and effectively solves the problems of wound leakage and artificial cornea detachment between the artificial cornea and the patient cornea. Meanwhile, the preparation method is simple, easy to operate and wide in market prospect.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a diagram illustrating the effect of the artificial cornea provided by the embodiment of the present invention after implantation.
Description of reference numerals:
1-artificial cornea, 2-original cornea of patient, 3-autologous or allogeneic lamellar cornea.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In the description of the present invention, it is to be understood that the terms "upper", "lower", "front", "rear", "left", "right", "top", "bottom", "inner", "outer", and the like, indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, are merely for convenience in describing the present invention and simplifying the description, and do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present invention.
Example (b):
the invention provides a preparation method of an artificial cornea in a corneal stroma, which comprises the following steps:
(1) preparing a dry silicon hydrogel mould blank: polymerizing a silicon hydrogel monomer into a dry silicon hydrogel mould blank:
s1, weighing the following raw materials in percentage by mass: 32% of silicon-containing monomer, 45% of hydrophilic monomer, 3.85% of cross-linking agent, 0.21% of light/heat initiator and the balance of solvent n-butyl alcohol;
s2, mixing and stirring the components uniformly according to the formula amount, injecting the mixture into a mold, and carrying out polymerization reaction under the conventional heating or ultraviolet lamp irradiation condition;
s3, placing the mold in an alcohol solvent with the volume fraction of 18% for separation, and collecting to obtain a silicon hydrogel mold blank;
s4, modifying the mold blank in isopropanol with the volume fraction of 16% for 1 h; the isopropanol is used as a cleaning degreaser, so that the grease material on the mould blank can be completely cleaned, the transparency of the mould blank is improved, and meanwhile, the channel on the mould blank is opened, so that the oxygen permeability coefficient of the mould blank is improved;
s5, soaking the modified mould blank with pure water for 1-3 times, then placing the mould blank in 0.9% of physiological saline for 50 minutes, finally sealing the mould blank in a penicillin bottle with 0.9% of physiological saline, and sterilizing to obtain a finished mould blank;
(2) turning and forming: fixing the dry-state silicon hydrogel model blank on a numerical control lathe, and sequentially turning a front plate and a light column part of the artificial cornea, wherein the curvature radius of the front plate is consistent with that of the front surface of the cornea, the central area of the front plate is thick, and the peripheral part of the front plate is gradually thinned;
(3) polishing and hydrating: and (3) polishing the front surface of the artificial cornea front plate and the back surface of the optical column part prepared in the step (2), and placing the artificial cornea front plate and the optical column part in normal saline for sufficient hydration and softening to form the colloidal artificial cornea.
In the step (2), the central thickness of the artificial cornea anterior plate is 70-100 microns, the peripheral part of the artificial cornea anterior plate is gradually thinned, and the diameter of the artificial cornea anterior plate is 5-8 mm.
In the step (2), the artificial cornea light pillar part has the diameter of 3-6mm and the length of 4-6 mm.
In the step (1), the silicon-containing monomer is formed by mixing methacryloxypropyltris (trimethylsiloxy) silane and poly (dimethylsiloxane) terminated bis (hydroxyalkyl) according to the mass ratio of 1: 1.
The hydrophilic monomer is N, N-diethyl (meth) acrylamide.
The artificial cornea prepared by the steps is transparent, and the writing below the cornea is clear and the edge is neat.
The artificial cornea implanting method comprises the following steps:
as shown in FIG. 1, if the patient has only lesions in the posterior (deep) or endothelial layer of the cornea, and the anterior cornea is still normal, the original cornea 2 of the patient is dissected before the artificial cornea 1 is implanted, within a range of 10X 10mm, and at a depth of 100 microns on average and 200 microns. A 3-5mm diameter trephine is used for drilling a rear implantation bed on a residual autologous or allogeneic lamellar cornea 3 of a patient, the artificial cornea 1 is implanted, a light column part of the artificial cornea 1 is embedded into an anterior chamber through a trephine opening, a front plate of the artificial cornea 1 is positioned between layers of the patient's cornea, and then anterior lamellar tissues of the patient cut off in the operation are covered and sutured and fixed on the surface of the artificial cornea 1.
If the patient's anterior cornea is diseased and not suitable for overlying and sutured fixation to the surface of the artificial cornea, a sheet of less cellular competent donor corneal tissue is used to overlie and sutured fixation, i.e., replacement by autologous or allogeneic lamellar cornea 3. Other surgical methods are similar to those described above.
The artificial cornea is implanted between the corneal tissue layers of a patient, a layer of autologous or allogeneic lamellar corneal tissue is covered on the surface of the artificial cornea, and the surface of the patient's cornea after an operation does not have a boundary between the artificial cornea and the patient's cornea, so that the leakage and the artificial cornea falling out after the operation are avoided. Unlike Boston's keratoprosthesis, which requires the use of a donor cornea with good cellular activity that can be used for penetrating corneal transplantation, the keratoprosthesis of the present invention does not require a donor cornea, or only requires lamellar corneal tissue with poor cellular activity that cannot be used for penetrating corneal transplantation, and such a donor cornea with poor cellular activity is not deficient.
Test example:
the prepared artificial cornea is used for 3 months after a lamellar keratoplasty of a monkey aged 4 years, the transparency of the central cornea is completely the same as that of the peripheral cornea, and the iris texture of the implantation area is clear and continuous with that of the peripheral cornea. And by HE staining showed: the stroma collagen fiber before the cornea has clear texture, the stroma cells of the cornea can grow into the collagen fiber, and the surface layer is covered by 3-5 layers of epithelial cells.
In short, the artificial cornea of the present invention is an integrated artificial cornea implanted in the corneal stroma, which can avoid wound leakage and artificial cornea prolapse after operation, and can be implanted without donor cornea or with only poor cell activity, and is easy to obtain donor cornea.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.
Claims (10)
1. A method for preparing an artificial cornea in a corneal stroma is characterized by comprising the following steps:
(1) preparing a dry silicon hydrogel mould blank: polymerizing a silicon hydrogel monomer into a dry-state silicon hydrogel mould blank;
(2) turning and forming: fixing the dry-state silicon hydrogel model blank on a numerical control lathe, and sequentially turning a front plate and a light column part of the artificial cornea, wherein the curvature radius of the front plate is consistent with that of the front surface of the cornea, the central area of the front plate is thick, and the peripheral part of the front plate is gradually thinned;
(3) polishing and hydrating: and (3) polishing the front surface of the artificial cornea front plate and the back surface of the optical column part prepared in the step (2), and fully hydrating and softening to form the colloidal artificial cornea.
2. The method of claim 1, wherein in step (1), the mold blank is made of silicone gel, hydrogel or polymethyl methacrylate (PMMA).
3. The method according to claim 1, wherein in the step (2), the artificial cornea is prepared such that the anterior plate has a central thickness of 70 to 100 μm and a peripheral portion which is gradually thinned and has a diameter of 5 to 8 mm; the artificial cornea light column part has the diameter of 3-6mm and the length of 4-6 mm.
4. The method of claim 1, wherein in the step (2), the keratoprosthesis molding method is a rotational molding method or a casting molding method.
5. The method for preparing an artificial cornea within a corneal stroma according to claim 1, wherein in the step (1), the method for preparing the dry-state silicone hydrogel mold blank comprises the following steps:
s1, weighing the following raw materials in percentage by mass: 23-40% of silicon-containing monomer, 36-52% of hydrophilic monomer, 0.05-8% of cross-linking agent, 0.05-5% of light/heat initiator and the balance of solvent;
s2, mixing and stirring the components uniformly according to the formula amount, injecting the mixture into a mold, and carrying out polymerization reaction under the conventional heating or ultraviolet lamp irradiation condition;
s3, placing the mold in an alcohol solvent with the volume fraction of 10-30% for separation, and collecting to obtain a silicon hydrogel mold blank;
s4, modifying the mold blank in isopropanol with the volume fraction of 10-20% for 1 h; the isopropanol is used as a cleaning degreaser, so that the grease material on the mould blank can be completely cleaned, the transparency of the mould blank is improved, and meanwhile, the channel on the mould blank is opened, so that the oxygen permeability coefficient of the mould blank is improved;
s5, soaking the modified mould blank with pure water for 1-3 times, then placing the mould blank in 0.9% physiological saline for 30-60 minutes, finally sealing the mould blank in a penicillin bottle with 0.9% physiological saline, and sterilizing to obtain a finished mould blank.
6. The method of claim 5, wherein the silicon-containing monomer is methacryloxypropyl tris (trimethylsiloxy) silane, (3-methacryloxy-2-hydroxypropoxy) propylbis (trimethylsiloxy) methylsilane, 1, 3-bis (3-methacryloxypropyl) tetrakis (trimethylsiloxy) disiloxane, poly (dimethylsiloxane) terminated bis (hydroxyalkyl), or a combination thereof.
7. The method of claim 5, wherein the hydrophilic monomer is alkyl (meth) acrylamide, N-ethyl (meth) acrylamide, N-vinylpyrrolidone, N-diethyl (meth) acrylamide, N-propyl (meth) acrylamide, N-2-hydroxyethyl (meth) acrylamide, and combinations thereof.
8. The method of claim 5, wherein the solvent is 1, 2-propanediol, n-butanol or n-hexanol.
9. The method of claim 1, wherein the hydration of the keratoprosthesis in the step (3) is softened in the presence of a physiological saline solution.
10. An artificial cornea produced by the method for producing an artificial cornea in corneal stroma according to any one of claims 1 to 9.
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