CN107007879A - A kind of active artificial cornea and preparation method thereof - Google Patents

Abstract

The present invention discloses a kind of active artificial cornea and preparation method thereof.The artificial cornea is the integral type synthesising macromolecule copolymer hydrogel structure containing gradient composition, includes central optical part and the peripheral part of bioactivity of biologically inert.It is transparent that the present invention prepares central optical, periphery has the artificial cornea base material of gradient hydrogel character, nano coating technology is used again, polyvinylidene fluoride is carried out in artificial cornea base material central part (interior outside), tetrafluoromethane, the coating and corona treatment of heptafluoro-propane, form inactive surfaces, collagen grafting is carried out to base material periphery again, micromolecule polypeptide and growth factor-induced activation, make base material bioactive process with it is engineered, finally obtain central optical excellent, periphery good biocompatibility, it is simple in construction, facilitating operation and the active artificial cornea that can exist steadily in the long term without abjection.Make to have on artificial cornea periphery and run through type pore space structure, be conducive to patient's eye to be brought into close contact with artificial cornea.

Description

A kind of active artificial cornea and preparation method thereof

technical field

The invention relates to an ophthalmic medical device, in particular to an active artificial cornea and a preparation method thereof.

Background technique

Corneal disease is currently the main blinding eye disease in the world, accounting for the second place in ophthalmology blinding eye disease. There are 32.37 million patients with corneal diseases in my country, and more than 4 million patients have been blinded. With the increase of trauma, chemical injury, infection and other patients, the number of blind patients is increasing by more than 100,000 every year. The best way to treat corneal diseases is corneal transplantation. Among these patients, the vast majority of people can regain their sight through corneal transplantation. However, due to the serious shortage of donor corneal materials, only about 5,000 patients can undergo corneal transplantation each year, accounting for only 2% of the cases that actually require surgery, which is far from meeting the needs of patients.

Corneal diseases not only make patients lose their ability to work, reduce the quality of life, cause physical and mental damage, but also cause serious losses and economic burdens to families, and have a great adverse impact on society. Therefore, the corneal substitute---artificial cornea has become an effective and feasible surgical approach to treat such diseases. Seeking an ideal artificial cornea has always been the dream of many patients, and it is also the direction of efforts of scientific and technological workers.

The artificial cornea is a special refractive device made of heterogeneous materials. It is surgically implanted into the affected eye to replace the cloudy and diseased corneal tissue, so as to maintain the integrity of the eyeball, remove infection lesions, restore corneal transparency, and obtain visual functions, etc. Purpose.

At present, the artificial corneas that have been clinically applied are all foreign products, including Boston artificial corneas, Pintcueei artificial corneas, Osteo-Odonto artificial corneas, Alphacor artificial corneas, and Strampelli artificial corneas. There is no independent artificial cornea product in my country that has been widely used clinically. The characteristics of these foreign products are as follows: (1) Boston artificial cornea (Dohlman type) needs to be installed on a fresh donor cornea graft, that is, the donor cornea is still needed to complete the treatment; the patient needs to wear a soft cornea after the operation Contact lenses to prevent tear evaporation from the eye and reduce depression of the artificial cornea, thereby reducing the possibility of donor corneal stent necrosis and melting; artificial corneal fibrous exudate membrane formation, glaucoma, persistent epithelial defects, aseptic vitritis, Endophthalmitis and retinal detachment are the most common complications after Boston artificial cornea, and the incidence rate of artificial corneal fibrous exudate membrane is as high as 24-65%. Moreover, in some patients postoperatively, complications such as leakage of the conjunctival flap, thinning and dissolution of the anterior corneal stroma, and even the discharge of the artificial cornea may occur. (2) The MICOF artificial cornea produced in Russia has a certain effect on chemical injury of the eye, but there are problems such as complicated surgical methods and many complications; (3) self-developed improved polyethylene glycol based on the Chirila Pros artificial cornea The methyl acrylate-polymethyl methacrylate integrated artificial cornea is still in the stage of animal testing.

Judging from the results of current applications, whether it is Boston, Osteo or Alphacor artificial cornea, the biocompatibility between the artificial material and the body, the complexity of the operation process, the long-term curative effect after operation, the prevention and treatment of various postoperative complications, The maintenance of optimal postoperative visual function still needs to be improved. These problems are the biggest obstacle to the vision recovery of corneal blind patients, and also the biggest threat to the postoperative visual acuity of patients. They also greatly limit the further development and wide application of artificial corneas. With the rapid development of social economy, people pay more and more attention to health. The development of medical equipment must be combined with modern technology to keep pace with the development of the times in order to meet people's growing demand for therapeutic effects.

At present, in terms of artificial cornea, the China Intellectual Property Office has authorized 18 invention patents and 22 public invention patents. Pore agent, the biocompatible polymer is dissolved in tetrahydrofuran to make a saturated solution, then mixed with the pore forming agent and then poured into the hollow cylindrical semi-finished product made in the ring mold, and then the initiator, crosslinking agent, biocompatible Pour the mixture of permanent polymer monomers into the semi-finished product for reaction, and then cut, polish and soak the artificial cornea blank to obtain the artificial cornea.

CN1128096C discloses a preparation method of biologically induced active artificial cornea, which specifically comprises dissolving chitosan in an acid solution, dissolving collagen and hyaluronic acid in water; dissolving chitosan acid solution and an aqueous solution of collagen and hyaluronic acid Stir at room temperature; add carbodiimide cross-linking agent, fibroblast growth factor, epidermal growth factor and cell transforming growth factor to the obtained mixture, and mix thoroughly for half an hour; inject the obtained mixture into the prefabricated cornea In the mold, fill the corneal mold, put it in an oven and dry it, and then take it out to obtain a corneal product; soak the corneal product obtained after washing and drying to remove residual impurities, and place it in water to obtain a biologically induced Active artificial cornea.

CN100340309C discloses a biologically induced active artificial cornea, the components include chitosan 0.5% to 3%, collagen 0.5% to 3%, hyaluronic acid 0.1% to 0.5%, water 93.5% to 98.8%, in order to help Stimulate the enrichment speed of autologous growth factor, and integrate corneal growth factor on the material.

CN102920532B discloses a kind of artificial cornea, comprises bracket and mirror column, and bracket extends along a spherical surface, and the center is provided with the bracket seat made of medical methyl methacrylate hole-like, and internal thread is arranged on inner wall; The diameter of mirror column The cross-section is circular; it includes a lead-in section, a threaded section and an exposed section that are sequentially connected and arranged coaxially; the peripheral surface of the threaded section has an external thread that cooperates with the internal thread, and when the bracket is matched with the mirror column, the convex surface The protruding direction of the bracket is consistent with the protruding direction of the bracket.

CN104368046B discloses a fiber-reinforced drug-loaded hydrogel artificial corneal skirt bracket and a preparation method thereof. The skirt bracket is composed of hydrophilic hydrogel, fibers and biodegradable drug-loaded microspheres, and the fiber content is 6-6 10%, the content of the biodegradable drug-loaded microspheres is 8-15%, the content of the hydrophilic hydrogel is 75-86%, and the fibers are randomly distributed in the hydrophilic hydrogel.

CN 1314461C discloses a bioactive artificial cornea, which includes an optical center and a peripheral frame. The peripheral frame is prepared from bioactive calcium salt, macromolecular polyvinyl alcohol and a solvent. Firstly, the polyvinyl alcohol is dissolved in the solvent, and the bioactive calcium salt is added Mix evenly to obtain a mixed solution, add a porogen to the mixture, place the mixture in a mold to form a hollow cylinder peripheral bracket, form an optical center in the inner cavity of the peripheral bracket, and remove the residual solvent and porogen in deionized water and other impurities.

CN100484497C discloses a preparation method of a biologically active artificial cornea, using animal corneal stroma as material, adopting enzyme digestion, repeated freezing and thawing, washing, Co-60 irradiation, and compounding to promote the growth of corneal cells or/and prevent the development of local lesions The artificial cornea is prepared through the steps of functional components.

CN101380486B provides a kind of active regenerative artificial corneal graft and its preparation method, the composition comprises chitosan, collagen, chondroitin sulfate, polyethylene glycol, polyvinyl alcohol and, triple distilled water, also includes appropriate amount of corneal cell growth factor, Fibronectin and laminin. Dissolving chitosan, collagen and sulfated cartilage in hydrochloric acid, acetic acid and water respectively, stirring and mixing the components in proportion at room temperature, pouring them into molds for drying, soaking in water, cleaning and drying to obtain artificial corneal products.

CN101843923B discloses a method for preparing a tissue-engineered artificial corneal endothelial carrier support using fresh amniotic membrane. First, the fresh amniotic membrane is soaked and sterilized in tobramycin sulfate solution, and after being inverted and digested by trypsin-EDTA digestion solution, lightly scraped with a cell scraper The epithelial surface of the amniotic membrane is completely removed from the residual epithelial cells to obtain the amniotic membrane without the epithelial layer. It can be used as a carrier scaffold for tissue engineering artificial corneal endothelium.

CN102580147B discloses an artificial cornea with antibacterial activity, comprising a porous peripheral stent and an optical center, the stent includes antibacterial chitosan derivatives, polyvinyl alcohol, and nano-phosphate, and the optical center includes polyvinyl alcohol Hydrogel, polyhydroxyethyl methacrylate hydrogel.

CN102755204B discloses a novel assembled artificial cornea, which includes a central optical part and a fixed support part. The optical part includes a spherical cover and a cylindrical transparent body. The upper surface of the spherical cover is a spherical surface, and the lower surface is connected to the upper surface of the transparent body. , the middle part of the support part is provided with a through hole, and a fixing ring is provided on the side wall of the through hole; the transparent body penetrates through the through hole to fix the support part.

CN103830021B discloses an artificial cornea and its preparation method, which includes a spherical corneal body optical functional area and a spherical band-shaped support area, the optical functional area and the support area are combined with each other, and the junction is an integrated transitional structure that interweaves and fuses with each other ; Among them, the optical functional area of the corneal body is made of polyhydroxyethyl acrylate hydrogel with good biocompatibility and light transmission, and the support area is made of PHEMA porous scaffold uniformly reinforced by silk fibers. The natural integration connection between them.

CN104436302B discloses a nano-ultra-thin biofilm differentially modified artificial cornea on the front and rear surfaces and its production method. The front surface of the optical part is repeatedly deposited with a polycation layer and an epidermal growth factor layer; the rear surface of the optical part is repeatedly deposited from the inside to the outside. A polycation layer and an HA layer are deposited, and the outermost layer is an HA layer. The preparation method includes making the surface of the artificial cornea negatively charged; making the polycation and epidermal growth factor alternately adsorbed on the front surface of the artificial cornea; making the polycation and HA alternately Adsorbed on the posterior surface of the artificial cornea, finally dried and sealed.

CN106139249A discloses a preparation method of a multi-component polymer artificial cornea, which includes synthesizing multi-component copolymer materials, preparing a three-dimensional corneal bracket, using a 3D bioprinter to print a three-dimensional bracket in the shape of the cornea, using ECM to functionally modify the three-dimensional bracket, and residual corneal microstructure. The artificial cornea was prepared through steps such as the construction of the tissue method.

CN105688282A discloses a new type of bioartificial cornea that induces cellularization in vivo and is rapidly transparent. The preparation method adopted includes acquisition of corneal raw materials, preparation of corneal stents, depth modification of corneal stents, deep corneal inactivation and depyrogenation, and corneal irradiation. Bacteria and corneal endothelial cells were cultured and planted to construct deep and shallow lamellar bioartificial corneas and full-thickness bioartificial corneas.

Because, in essence, in order to obtain a clinically applicable and stable artificial cornea, two major problems need to be solved:

(1) Excellent biocompatibility between artificial cornea and human eye:

Many artificial corneal materials, due to the use of polymer materials, metals or inorganic materials, lead to insufficient biocompatibility, immune reactions, etc., causing inflammation, corneal dissolution, and prolapse of the artificial cornea. The fundamental reason is that artificial materials cannot interact with the host. The cornea produces ideal biological healing.

(2) Maintain the optical transparency and biological inertness of the center of the artificial cornea (fitting the pupil): some materials overcome the lack of biocompatibility and can fit closely with the human eye. However, due to cell growth and newborn The growth of blood vessels, or the adhesion and deposition of other substances in the eye, causes the formation of anterior and posterior membranes, so that the central part of the corneal material will gradually lose optical transparency after a period of time, and cannot maintain the best visual function, resulting in the failure of the artificial corneal material.

However, from the existing patents and products, there are generally the following deficiencies:

(1) The existing patents seldom take into account the biocompatibility of the artificial cornea periphery, use less active ingredients that can promote the growth of peripheral corneal cells, and do not consider the use of gradient hydrogel as the corneal peripheral material importance;

(2) Most artificial corneas adopt an integrated design, and the central optical part is also compounded with hydrogel components, which can easily cause some cells and new blood vessels to grow in, or the adhesion and deposition of other substances in the eye, resulting in the anterior and posterior membranes. form, gradually lose their transparency;

(3) In the existing artificial cornea patents, the central part of the designed cornea has not been treated with biological inertization.

Contents of the invention

In order to overcome the shortcomings and deficiencies of the prior art, the primary purpose of the present invention is to provide an active artificial cornea. The present invention provides a new type of artificial cornea with optical transparency in the center and biological activity in the periphery. The artificial cornea base material with optical transparency in the center and gradient hydrogel characteristics in the periphery is prepared by gradient ultraviolet irradiation polymerization technology, and then nano-coating Coating and plasma treatment of polyvinylidene fluoride, tetrafluoromethane, and heptafluoropropane are carried out on the central part (inside and outside) of the artificial cornea substrate to form an inert surface, and collagen grafting and small molecule Peptides and bFGF induce activation, bioactivate the substrate and engineer the tissue, and finally obtain an active artificial cornea with excellent central optical properties, good peripheral biocompatibility, simple structure, convenient operation, and long-term stable existence without prolapse.

Another object of the present invention is to provide a method for preparing the above active artificial cornea.

The object of the present invention is achieved through the following technical solutions:

An active artificial cornea is a one-piece synthetic polymer hydrogel structure with gradient components, including a biologically inert central optical part and a biologically active peripheral part.

The high molecular polymer is a polymer of acrylic acid derivatives, specifically including a polymer of methyl methacrylate and a copolymer of hydroxyethyl methacrylate-acrylic acid.

Described gradient composition means that the content of the high polymer that forms the whole artificial cornea is distributed in a gradient in different parts, specifically the central optical part, that is, the artificial cornea close to the pupil position, and its composition is pure PMMA (methyl methacrylate polymer, namely: polymethyl methacrylate), with a diameter of 5 mm; away from the central part, its PMMA content gradually decreases, and the content of P (HEMA-AAS) (copolymer of hydroxyethyl methacrylate-acrylic acid) gradually decreases. Increase, when reaching the periphery, the PMMA content is 0, all are P(HEMA-AAS), and the change of the gradient is that every time the radius increases by 0.5 mm, the PMMA content decreases by 15%, and the P(HEMA-AAS) content increases by 15%.

The composition of the biologically inert central optical part is the polymer PMMA, which is then coated with a transparent fluorine-containing compound to obtain an optical part that can not only maintain optical transparency but also have biological inertness.

For the coating of transparent fluorine-containing compounds, at first, a polyvinylidene fluoride coating of 50 to 200 nanometers is coated on the polymer PMMA to form a nano-fluoroplastic coating, and then plasma technology is used to further coat the coating on the coating. Coating tetrafluoromethane, heptafluoropropane coatings of 30-80 nanometers, and producing a biologically inert layer by double-layer coating.

The main body of the biologically active peripheral part is composed of P(HEMA-AAS) hydrogel, which contains a penetrating hole structure, part of which is compounded with molecules through grafting, and is loaded with biologically active components.

The hole structure is obtained by excimer laser processing technology, and the hole diameter is 160-200 nanometers, and the hole distribution is denser near the outer diameter, and the hole is less near the central part.

Said grafting and compounding of molecules, loaded with bioactive components: first graft collagen on the main body of the hydrogel, then carry out self-assembly of small molecule polypeptides, and then compound growth factors on the surface of the polypeptides.

The small molecular polypeptides are V ₆ D ₂ (small molecular peptides containing valine and aspartic acid) and ALPs (small molecular peptides containing alanine, leucine, proline and serine). peptide complexes.

The growth factor is at least one of bFGF, EGF and the like. Wherein, bFGF refers to basic fibroblast growth factor, and EGF refers to epidermal growth factor.

A method for preparing an active artificial cornea, comprising the steps of:

The first step: using acrylic acid derivatives as raw materials, using a photoinitiator to induce free radicals, and adopting a layered gradient ultraviolet radiation polymerization technology, an artificial cornea substrate with gradient hydrogel properties is prepared. The center of the substrate ( The part that fits the pupil of the human eye, with a diameter of 5 mm) is pure PMMA, and as the radius expands, the content of PMMA components gradually decreases, and the content of P (HEMA-AAS) gradually increases. P (HEMA-AAS) hydrogel The structure keeps the cornea moist and beneficial to the growth of corneal cells and fusion with the human cornea. Then, excimer laser processing technology is used to perforate layer by layer to obtain a reasonable pore structure. The porous scaffold has characteristics similar to extracellular matrix, which can support cell growth, proliferation and secretion of extracellular matrix, so that it can heal with the host cornea One piece, it can stably support the center of the base material (optical part) to achieve long-term retention. As shown in Figure 1.

The acrylic acid derivatives are (sodium) acrylic acid (AAS), methyl methacrylate (MMA), and hydroxyethyl methacrylate (HEMA).

The second step: In order to reduce the biological activity of the central part of the artificial cornea, we use nano-coating technology to process polyvinylidene fluoride coating on the central part (inside and outside) of the artificial cornea substrate to form a nano-fluoroplastic coating , and then further conduct tetrafluoromethane and heptafluoropropane plasma treatment on the coating to form an inert surface at the center of the substrate, so that the optical part does not absorb cells, and prevents cells from growing into, new blood vessels from growing into, or other substances in the eye. Adhesion and deposition, to avoid the common front and rear film formation of other materials, to ensure the long-term stable visual function of this part.

The third step: avoiding the central part, carry out collagen grafting on the periphery of the substrate, and then carry out self-assembly of small molecular polypeptides (complexes of two peptides of V ₆ D ₂ and ALPs), and conduct bFGF and EGF molecular compound adhesion. Attached, the substrate is bioactivated and tissue engineered to obtain an artificial cornea that is highly compatible with the patient.

As a preferred solution, the bFGF, EGF growth factor, and small molecule polypeptide active ingredients used in the present invention are produced by the National Engineering Center for Genetic Engineering Drugs of Jinan University, or produced by Guangdong Nanhai Langtai Pharmaceutical Co., Ltd.

As a preferred solution, the polyvinylidene fluoride used in the present invention is a polyvinylidene fluoride product produced by DuPont of the United States or Mitsubishi of Japan.

As a preferred solution, tetrafluoromethane and heptafluoropropane used in the present invention are produced by Foshan Kedi Gas Chemical Co., Ltd.

Compared with the prior art, the present invention has the following advantages and effects:

(1) Adopt gradient functional material preparation technology, and use gradient layered casting ultraviolet light polymerization method to prepare integrated artificial cornea matrix material with gradient MMA-HEMA-AAS component content. The center (center) of the substrate close to the pupil is PMMA , as the radius expands, the proportion of PMMA decreases gradually, and the proportion of P(HEMA-AAS) gradually increases. When it reaches the periphery of the substrate, it is all P(HEMA-AAS), so as to solve the problem of artificial cornea strength and hydrogel biocompatibility The matching problem of the artificial cornea can exist stably for a long time in the body.

(2) Using excimer laser processing technology, a penetrating hole structure is made around the artificial cornea. The reasonable hole structure and distribution provide support for the growth of host corneal cells, which is conducive to the close attachment of the patient's eyes to the artificial cornea.

(3) The nano-coating technology of polyvinylidene fluoride transparent material, tetrafluoromethane and heptafluoropropane plasma are used to inertize the central part (inside and outside) of the artificial cornea, so that the central optical part of the artificial cornea remains inert, and the cells With the inability of blood vessels to grow in, proteins and other secretions cannot adhere to the optical part to maintain optimal visual function.

(4) Using "grafting-composite" technology, I-type collagen, small molecular polypeptide and basic fibroblast growth factor (bFGF) were fixed on the peripheral surface of the artificial cornea to obtain an active coating with biological induction. After entering the body, it can actively mobilize favorable factors in the body and regulate the biological behavior of host cells.

Description of drawings

Fig. 1 is an overall view of the artificial cornea of the present invention; wherein, (1)-central optical part, (2)-peripheral hydrogel active part with holes.

detailed description

The present invention will be further described in detail below in conjunction with the embodiments and the accompanying drawings, but the embodiments of the present invention are not limited thereto.

Using acrylic acid, methyl methacrylate, and hydroxyethyl methacrylate as raw materials, adding photoinitiators, through layered gradient ultraviolet radiation polymerization technology, the artificial cornea substrate with gradient hydrogel properties is prepared. The substrate’s The central part (fitting with the pupil of the human eye, with a diameter of 5 mm) is pure PMMA, and the periphery expands with the radius. For every increase of 0.5 mm, the content of PMMA components decreases by 15%, and the content of P (HEMA-AAS) increases by 15%. The PMMA component content until the outer portion was zero, and the P(HEMA-AAS) content was 100%. Then, polyvinylidene fluoride coating is carried out on the central part (inside and outside) of the artificial cornea substrate to form a nano-fluorine plastic coating, and then the coating is further treated with tetrafluoromethane and heptafluoropropane plasma, The central part of the material forms an inert surface. Finally, the excimer laser processing technology is used to perforate the periphery, and then the self-assembly of collagen grafts and small molecule polypeptides (complexes of V ₆ D ₂ and ALPs peptides) is carried out. And compound bFGF molecules to obtain an artificial cornea that is highly biocompatible with the patient.

Select 10 Japanese big-eared white rabbits for 3 months, carry out modeling by alkali burn, and then implant the artificial cornea of the present invention, and observe the recovery of the cornea under a microscope within a period of time, and set the observation indicators as follows: ①Artificial cornea 2. the occurrence of secondary glaucoma; 3. the occurrence of proliferative membranes before and after the artificial cornea; 4. the occurrence of endophthalmitis; 5. the dissolution of the cornea. The in-position time and in-position rate meet the requirements; the incidence rate of secondary glaucoma is small, and the incidence rate meets the statistical requirements; through the treatment of fluorine-containing compounds, the artificial cornea of the present invention basically does not appear proliferative film; within one week after implantation, there will be Slight endophthalmitis then disappears gradually; no corneal dissolution occurs, indicating that the artificial cornea prepared by the present invention has better applicability.

The above-mentioned embodiment is a preferred embodiment of the present invention, but the embodiment of the present invention is not limited by the above-mentioned embodiment, and any other changes, modifications, substitutions, combinations, Simplifications should be equivalent replacement methods, and all are included in the protection scope of the present invention.

Claims (10)

1. a kind of active artificial cornea, it is characterised in that：The artificial cornea is the integral type synthesis polyphosphazene polymer containing gradient composition Compound hydrogel structure, includes central optical part and the peripheral part of bioactivity of biologically inert.

2. active artificial cornea according to claim 1, it is characterised in that：

Described high molecular polymer is the polymer of acrylic acid derivative, specifically includes the polymer of methyl methacrylate, The copolymer of hydroxyethyl methacrylate-acrylic acid.

3. active artificial cornea according to claim 1, it is characterised in that：

Described gradient components refer to content distribution gradient of the high polymer in different parts for constituting whole artificial cornea, specifically For central optical position, that is, press close to the artificial cornea of pupil position, its composition is pure PMMA, a diameter of 5 millimeters；Leave central portion Position, its PMMA content is gradually reduced, and P (HEMA-AAS) content gradually increases, during to periphery, and PMMA contents are 0, all P (HEMA-AAS), the change of gradient turns to radius and often increases 0.5 millimeter, and the content that PMMA contents decline 15%, P (HEMA-AAS) increases Plus 15%.

4. active artificial cornea according to claim 1, it is characterised in that：

The composition of the central optical part of described biologically inert is polymer P MMA, and transparent fluorochemical is coated with above, Both optical transparence is kept, the opticator for also possessing biologically inert.

5. active artificial cornea according to claim 4, it is characterised in that：

The transparent fluorochemical of described coating, first, coats 50~200 nanometers of polyvinylidene fluoride on polymer P MMA Coating, forms nanometer plastic coating of fluoride, then using plasma technology, on the coating layer the four of further 30~80 nanometers of coating Fluoromethane, heptafluoro-propane coating, biologically inert layer is produced by bilayer coating.

6. active artificial cornea according to claim 1, it is characterised in that：

The peripheral part of described bioactivity, its main body is made up of P (HEMA-AAS) hydrogel, wherein containing through hole Structure, its part is combined by grafting with molecule, is loaded with bioactive ingredients.

7. active artificial cornea according to claim 6, it is characterised in that：

The aperture of described pore space structure is 160~200 nanometers, and pore size distribution is big in outer footpath position density, by middle body hole Hole is few.

8. active artificial cornea according to claim 6, it is characterised in that：

Described is combined by grafting with molecule, is loaded with bioactive ingredients：Collagen first is grafted in hydrogel main body, so The self assembly of micromolecule polypeptide, then the growth factor on polypeptide surface is compound are carried out afterwards.

9. active artificial cornea according to claim 8, it is characterised in that：

Described micromolecule polypeptide is V₆D₂With the compound of two kinds of peptides of ALPs.

10. active artificial cornea according to claim 8, it is characterised in that：

Described growth factor is at least one of bFGF and EGF.