阅读说明：本技术 一种氧化石墨烯增强胶原膜角膜修复材料及其制备方法 (Graphene oxide reinforced collagen membrane cornea repair material and preparation method thereof ) 是由 刘杨 于 2021-08-26 设计创作，主要内容包括：本发明公开了一种氧化石墨烯增强胶原膜角膜修复材料及其制备方法,包括以下步骤：(1)在25℃下,将牛腱胶原溶解于醋酸中,配制一定浓度的胶原溶液；(2)分别配制一定浓度的氧化石墨烯溶液、碳化二亚胺和N-羟基丁二酰溶液；(3)将步骤(2)得到的氧化石墨烯溶液缓慢加入到(1)得到的胶原溶液中,同时加入对应比例的碳化二亚胺和N-羟基丁二酰溶液,在一定温度下缓慢搅拌进行交联反应；(4)将步骤(3)得到的交联水凝胶自然风干后,即得到一种氧化石墨烯增强胶原膜角膜修复材料。本材料具有较好的力学性能、光学性能和生物相容性,并且成型可控,可用于临床上角膜组织的修复和替代,其制备工艺简单,设备简易。(The invention discloses a graphene oxide reinforced collagen membrane cornea repair material and a preparation method thereof, and the graphene oxide reinforced collagen membrane cornea repair material comprises the following steps: (1) dissolving bovine tendon collagen in acetic acid at 25 ℃ to prepare a collagen solution with a certain concentration; (2) respectively preparing a graphene oxide solution, carbodiimide and an N-hydroxysuccinimide solution with certain concentrations; (3) slowly adding the graphene oxide solution obtained in the step (2) into the collagen solution obtained in the step (1), simultaneously adding carbodiimide and N-hydroxysuccinimide solutions in corresponding proportions, and slowly stirring at a certain temperature to perform a crosslinking reaction; (4) and (4) naturally air-drying the crosslinked hydrogel obtained in the step (3) to obtain the graphene oxide reinforced collagen membrane cornea repair material. The material has better mechanical property, optical property and biocompatibility, controllable forming, simple preparation process and simple equipment, and can be used for clinically repairing and replacing corneal tissues.)

1. The preparation method of the graphene oxide reinforced collagen membrane cornea repair material is characterized by comprising the following steps:

(1) dissolving bovine tendon collagen in acetic acid at 25 ℃ to prepare a collagen solution with a certain concentration;

(2) respectively preparing a graphene oxide solution, carbodiimide and an N-hydroxysuccinimide solution with certain concentrations;

(3) slowly adding the graphene oxide solution obtained in the step (2) into the collagen solution obtained in the step (1), simultaneously adding carbodiimide and N-hydroxysuccinimide solutions in corresponding proportions, and slowly stirring at a certain temperature to perform a crosslinking reaction;

(4) and (4) naturally air-drying the crosslinked hydrogel obtained in the step (3) to obtain the graphene oxide reinforced collagen membrane cornea repair material.

2. The method according to claim 1, wherein the concentration of the collagen solution in the step (1) is 3.5 to 10 mg/mL.

3. The preparation method according to claim 1, wherein the concentration of the graphene oxide solution in the step (2) is 0.01 to 0.1 μ g/mL.

4. The method for preparing according to claim 1, wherein the collagen in the step (3): the mass ratio of the graphene oxide is 10-30: 1.

5. The method according to claim 1, wherein the stirring reaction in the step (3) is carried out at a temperature of 3 to 8 ℃.

6. The preparation method according to claim 1, wherein a certain amount of carbodiimide and N-hydroxysuccinimide solution is added in the step (3), and the mass ratio of (collagen + graphene oxide): carbodiimide (B): n-hydroxysuccinyl ═ 6:1: 1.

7. A graphene oxide reinforced collagen membrane cornea repair material prepared by the method of any one of claims 1 to 7.

Technical Field

The invention relates to a graphene oxide reinforced collagen membrane cornea repair material and a preparation method thereof, in particular to a method for preparing a cornea repair material with good physicochemical property and biocompatibility. The material obtained by the invention can be applied to the clinical corneal defect repair and replacement.

Background

The cornea is the outermost transparent tissue of the human eye and has the physiological functions of protecting the eyeball, sensing the environment, external stimulation and the like. Keratopathy is a common and frequently encountered disease in ophthalmology, is also one of the main blinding diseases, and is second only to cataract. At present, the patients with global keratopathy are increased at the speed of 150-. Although most of the patients with corneal blindness can be seen by corneal transplantation in clinic, due to the serious shortage of donated corneas, only 5000 corneal transplantation operations are completed in China every year. The lack of corneal repair material has become a bottleneck limiting the visibility of patients with corneal blindness.

Collagen is one of the main components of corneal tissue, and is the first choice material of corneal repair materials in tissue engineering due to its low immunogenicity, good biocompatibility and biodegradability. However, for many collagen-based corneal repair materials available, one of the major challenges is the insufficient mechanical properties of the materials. Such materials are not stably anchored to the ocular surface because they cannot withstand the suturing of extremely fine ophthalmic surgical sutures, which tend to tear during corneal transplantation procedures. According to the preparation method, the mechanical property of the collagen membrane material is improved by introducing the graphene oxide component into the material, so that the problem that the cornea repair material cannot tolerate surgical suture is solved.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides a graphene oxide reinforced collagen membrane cornea repair material and a preparation method thereof.

The purpose of the invention is realized by the following technical scheme:

a preparation method of a graphene oxide reinforced collagen membrane cornea repair material comprises the following steps:

(1) dissolving bovine tendon collagen in acetic acid at 25 ℃ to prepare a collagen solution with a certain concentration;

(2) respectively preparing a graphene oxide solution, carbodiimide and an N-hydroxysuccinimide solution with certain concentrations;

(3) slowly adding the graphene oxide solution obtained in the step (2) into the collagen solution obtained in the step (1), simultaneously adding carbodiimide and N-hydroxysuccinimide solutions in corresponding proportions, and slowly stirring at a certain temperature to perform a crosslinking reaction;

(4) and (4) naturally air-drying the crosslinked hydrogel obtained in the step (3) to obtain the graphene oxide reinforced collagen membrane cornea repair material.

Further, the concentration of the collagen solution in the step (1) is 3.5-10 mg/mL.

Further, the concentration of the graphene oxide solution in the step (2) is 0.01-0.1 [ mu ] g/mL.

Further, collagen in step (3): the mass ratio of the graphene oxide is 10-30: 1.

Further, the stirring reaction temperature in the step (3) is 3-8 ℃.

Further, adding a certain amount of carbodiimide and N-hydroxysuccinimide solution in the step (3), wherein the mass ratio of (collagen + graphene oxide): carbodiimide (B): n-hydroxysuccinyl ═ 6:1: 1.

The graphene oxide reinforced collagen membrane cornea repair material obtained by the invention can effectively improve the mechanical property of the collagen membrane, thereby improving the problem that the collagen-based cornea repair material cannot tolerate suture of an ophthalmic surgery suture, and providing more convenience for the material in clinical surgery operation and application.

Detailed Description

The invention will be further described with reference to the following examples for a better understanding of the invention, but the scope of the invention as claimed is not limited to the scope represented by the examples mentioned.

Example 1

(1) Dissolving bovine tendon collagen in acetic acid at 25 ℃ to prepare a collagen solution with the concentration of 6.5 mg/mL;

(2) respectively preparing a graphene oxide solution with the concentration of 0.05 mu g/mL, carbodiimide with the concentration of 15mg/mL and an N-hydroxysuccinimide solution with the concentration of 15 mg/mL;

(3) slowly adding the graphene oxide solution obtained in the step (2) into the collagen solution obtained in the step (1), and controlling the mass ratio of collagen: and (3) adding a certain amount of carbodiimide and N-hydroxysuccinimide solution into the graphene oxide at a ratio of 20:1, and controlling the mass ratio of (collagen + graphene oxide): EDC: NHS 6:1:1, and stirring at 4 ℃ to perform a crosslinking reaction;

(4) and (4) naturally air-drying the crosslinked hydrogel obtained in the step (3) to obtain the novel graphene oxide modified cornea repair material.

Example 2

(1) Dissolving bovine tendon collagen in acetic acid at 25 ℃ to prepare a collagen solution with the concentration of 7.5 mg/mL;

(2) respectively preparing a graphene oxide solution with the concentration of 0.06 mug/mL, carbodiimide with the concentration of 15mg/mL and an N-hydroxysuccinimide solution with the concentration of 15 mg/mL;

(3) slowly adding the graphene oxide solution obtained in the step (2) into the collagen solution obtained in the step (1), and controlling the mass ratio of collagen: and (3) adding a certain amount of carbodiimide and N-hydroxysuccinimide solution into the graphene oxide at a ratio of 20:1, and controlling the mass ratio of (collagen + graphene oxide): EDC: NHS 6:1:1, and stirring at 6 ℃ to perform a crosslinking reaction;

(4) and (4) naturally air-drying the crosslinked hydrogel obtained in the step (3) to obtain the graphene oxide reinforced collagen membrane cornea repair material.