KR101322337B1 - Silk artificial membrane for artificial dural membrane and biological membrane with excellent flexibility and solidity - Google Patents
Silk artificial membrane for artificial dural membrane and biological membrane with excellent flexibility and solidity Download PDFInfo
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- KR101322337B1 KR101322337B1 KR20100133134A KR20100133134A KR101322337B1 KR 101322337 B1 KR101322337 B1 KR 101322337B1 KR 20100133134 A KR20100133134 A KR 20100133134A KR 20100133134 A KR20100133134 A KR 20100133134A KR 101322337 B1 KR101322337 B1 KR 101322337B1
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- artificial
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- salt
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
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- D—TEXTILES; PAPER
- D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
- D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
- D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
- D04H1/04—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres having existing or potential cohesive properties, e.g. natural fibres, prestretched or fibrillated artificial fibres
- D04H1/08—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres having existing or potential cohesive properties, e.g. natural fibres, prestretched or fibrillated artificial fibres and hardened by felting; Felts or felted products
- D04H1/09—Silk
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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
- A61F2/0063—Implantable repair or support meshes, e.g. hernia meshes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction
Abstract
The present invention relates to a silk artificial membrane for artificial brain dural and biological membranes excellent in flexibility and suture strength, characterized in that consisting of silk fibroin and salt.
According to the present invention, the concern about the stability of the artificial membrane is avoided, the procedure and the treatment are easy because the flexibility and the bonding strength are excellent, and the thickness can be adjusted because the thick membrane of 300 µm or more can be produced.
Description
The present invention relates to silk artificial membranes for artificial brain dural and biological membranes, and more particularly, to artificial membranes and artificial membranes for artificial membranes having excellent flexibility and susceptibility for easy treatment and treatment.
Covering the inner surface of the skull and projecting between the cerebral hemispheres and the cerebrum and cerebellum, between the brain and the pituitary gland inevitably damaged during brain surgery.
For this reason, the amount of artificial dura mater replacing the damaged dura mater is increasing, but a market of 1 trillion in the world and a market of 30 billion in Korea are formed.
Among the materials for the dura mater, human-derived dura mater is currently prohibited due to the high possibility of infection with Creutzfeldt-Jakob disease.
In recent years, artificial brain dural membranes prepared using animal (cow) -derived collagen have been used in clinical practice.
In Korean Patent Publication No. 10-100461475, a collagen material composed of a laminate in which a collagen ultrafine fibrous nonwoven multilayer body is sandwiched between non-fibrous collagen layers is used to remove defects of biological membranes such as the brain dura, pericardium, pleural cavity, peritoneum, or intestinal membrane. It is proposed to be used as a supplementary material.
Korean Patent Laid-Open Publication No. 10-2001-0052714 fills a matrix that is biocompatible and capable of being decomposed and absorbed in vivo in a matrix, which is a nonwoven polymorphic structure of collagen fibers based on collagen ultrafine fibers. Or synthetic collagen material, including artificial neural tube, artificial spinal cord, artificial esophagus, artificial organ, artificial blood vessel, artificial valve, artificial dura mater, artificial ligament, artificial ligament, artificial gun, surgical suture, surgical filler, surgical reinforcement material, It is proposed to be applied to wound protectors, artificial skin or artificial cornea.
However, the artificial brain dense produced using animal (cow) -derived collagen has a serious problem of susceptible infection such as mad cow disease.
Despite such serious defects, there is no substitute to replace artificial dura mater using animal-derived collagen. Currently, the artificial dural material using synthetic biomaterials, which are mainly developed, is mechanically secured such as biosafety and suture strength. It is not yet commercialized due to problems such as strength.
Disclosure of Invention An object of the present invention is to provide a silk artificial brain dura mater and a silk artificial membrane for biological membranes, which are excellent in flexibility and suture strength, and are easily treated and treated.
Silk artificial membrane of the present invention for achieving the above object includes silk fibroin and salt.
The silk artificial film of the present invention is preferably composed of 50.00 to 99.99% by weight of silk fibroin and 0.01 to 50.00% by weight of salt.
The salt is preferably used any one of calcium chloride, sodium chloride, potassium chloride, sodium acetate.
On the other hand, the method for producing a silk artificial film of the present invention comprises the step of mixing the mixture of 50.00 to 99.99% by weight of silk fibroin 0.01 to 50.00% by weight of salt to make a mixed solution and pouring the mixed solution into a flat container and dried to produce a silk artificial film .
In the drying step, it is preferable to dry the mixed solution contained in the container in a constant temperature room containing 20 ~ 80 ℃, 20 ~ 80% moisture.
According to the present invention, concerns about the stability of the artificial membrane are eliminated, and the flexibility is greatly enhanced, so that the procedure and the treatment are easy.
In addition, since a thick film of 300 µm or more can be produced, the thickness can be adjusted.
In addition, the procedure is easier because it is not only flexible but also transparent and has excellent suture strength.
In addition, there is no cytotoxicity, and it is waterproof to protect the spinal cord and prevent leakage of cerebrospinal fluid.
1 is a graph showing the elongation rate of the silk artificial brain dura as an example of the silk artificial membrane of the present invention.
2 is a cross-sectional and surface photographic view of the silk artificial brain dura as an example of the silk artificial membrane of the present invention.
Figure 3a is a photographic view showing the transparency of the silk artificial brain dura as an example of the silk artificial membrane of the present invention.
Figure 3b is a view showing the transparency of the artificial dura mater made from conventional proprietary collagen.
Figure 4 is a photographic view showing the flexibility of the silk artificial brain dura as an example of the silk artificial membrane of the present invention.
5 is a photographic view showing the suture strength of the silk artificial brain dura as an example of the silk artificial membrane of the present invention.
Figure 6a is a graph showing the cytotoxicity results of silk artificial brain dura, an example of the silk artificial membrane of the present invention in 24 hours culture.
Figure 6b is a graph showing the cytotoxicity results of silk artificial brain dura, an example of the silk artificial membrane of the present invention at 48 hours culture.
Figure 6c is a graph showing the cytotoxicity results of silk artificial brain dura, an example of the silk artificial membrane of the present invention in 72 hours culture.
Hereinafter, preferred embodiments of the present invention will be described.
The silk artificial membrane of this invention consists of silk fibroin and a salt.
Silk fibroin is a protein that, together with sericin, forms a cocoon (silk).
Silk fibroin is relatively evenly present in 18 amino acids. Unlike the keratin protein of wool fibers, silk fibroin has a high content of glycine and alanine.
Among the amino acids of the collagen protein, the major protein that constitutes the human skin, glycine and alanine are the most abundant in the fibroin protein.
The fibroin protein having an amino acid structure similar to that of human skin has excellent biocompatibility and exhibits no inflammatory effect.
For this reason, the silk artificial film of this invention which has silk fibroin as a main component can dispel the concern about stability.
Salt, which is another main component of the silk artificial film of the present invention, makes the silk artificial film of the present invention flexible by making flexible the stiff symptoms occurring when a thick film is made only with silk fibroin.
In addition, the salt increases the strength of the silk artificial membrane of the present invention.
In addition, the salt may be any salt-based material, it is preferable to use any one of calcium chloride, sodium chloride, potassium chloride, sodium acetate.
After all, the silk artificial membrane of the present invention is very easy to perform the procedure and treatment because of its excellent flexibility and strength, in particular, because it has a very good suture strength and further has a waterproof property to prevent the leakage of cerebrospinal fluid and protection of the spinal cord, It is very suitable for use as a silk artificial brain dura mater.
In addition, since the silk artificial membrane of the present invention has transparency, it enables safe treatment during surgery, and because it is safe to use, there is no cytotoxicity and thus there is no problem in using it as a biofilm widely.
In addition, since the silk artificial film of the present invention can have a thickness of 300 μm or more, the thickness can be adjusted.
Such a silk artificial film of the present invention is preferably composed of 50.00 to 99.99% by weight of silk fibroin, and 0.01 to 50.00% by weight of salt.
If the silk fibroin is less than 50.00% by weight, there is a problem in forming the film. If the silk fibroin is more than 99.99% by weight, the flexibility of the film is lowered. Therefore, the silk artificial film of the present invention preferably contains 50.00 to 99.9% by weight of silk fibroin.
In addition, if the salt is less than 0.01% by weight, there is a problem that the flexibility of the film is lowered. If the salt is more than 50.00% by weight, the silk fibroin has a problem of forming a film, and therefore, the silk artificial film of the present invention has a salt of 0.01 to 50.00% by weight. It is good to contain.
Such a silk artificial film of the present invention is prepared by mixing 0.01 to 50.00% by weight of a liquid salt with 50.00 to 99.99% by weight of liquid silk fibroin to make a mixed liquid, and pouring the mixed liquid into a flat container and drying it.
The following Examples and Experimental Examples are only illustrative of the present invention, and the scope of the present invention is not limited by the Examples and Experimental Examples.
<Example 1> Silk artificial brain dura
A silkworm cocoon was used as a sample and refined at 100 ° C. with Marise oil soap to remove sericin.
The refined silk was dissolved in calcium chloride, ethanol, and calcium chloride-alcohol-aqueous solution prepared in water 1: 2: 8 (molar ratio) at 80 ° C. for 20 minutes.
This aqueous silk solution was placed in a dialysis membrane (MWCO = 12,000) and dialyzed in distilled water for 3 days to remove salt and ethanol.
The final concentration of the silk fibroin solution produced was about 2.5% and concentrated using PEG 20,000 (polyethylene glycol) to a concentration of 7 ~ 8%.
Add 0.01 to 50.00% by weight of calcium chloride solution to 50.00 ~ 99.99% by weight of the concentrated silk fibroin solution and mix well using a stirrer. An artificial silk dura was prepared as an example of the present invention.
Experimental Example 1 Structural Characteristics and Physical Properties of Silk Artificial Brain Dural
The thickness of the artificial dura, which is an example of the present invention produced in Example 1, was measured using a thickness gauge, and the structure was observed by FT-IR analysis.
Surface and cross-sectional structures were observed using a scanning electron microscope (SEM).
Tensile strength and elongation at break of the silk artificial brain dura, which is an example of the present invention prepared in Example 1, were measured using a tensile strength tester.
Experimental Example 2 Cell Culture and Cytotoxicity Experiment
For cytotoxicity testing, L929 fibroblasts were purchased from ATCC and incubated for 24 hours after inoculation with 10,000 cells per well in MEM medium containing 10% bovine serum, 50 μg / ml streptomycin and 100 U / ml penicillin. It was.
The silk artificial brain dura, an example of the present invention prepared in Example 1, was cut into 1 × 1 cm, and 10 ml of medium was added to 1 g of the dural sample, and eluted in a 37 ° C. CO 2 incubator for 24 hours.
The eluted samples were serially diluted with media and then treated with pre-cultured cells, and cell viability was evaluated using the MTT method.
<Result 1> Production result of silk artificial brain dura
Silk brain dura mat made of only silk fibroin has transparency but strong thickness 300 micrometers or less. However, the silk artificial brain dura, which is an example of the present invention produced in Example 1, can be adjusted to a thickness of 300 μm or more, and even 500 μm or more.
In the case of producing a silk artificial brain dura using a conventional manufacturing method of the artificial brain dural with silk fibroin, when the silk artificial brain dura has a thickness of 300 μm or more, transparency, which is a strength, disappears, but the present invention maintains transparency and thick silk artificial brain dura Can be produced.
<Result 2> Structural Characteristics and Physical Properties of Silk Artificial Brain Dural
Silk artificial brain dural, which is an example of the present invention produced in Example 1 has flexibility, elasticity and suture strength as shown in Table 1 and the graph of Fig. 1, the cross-sectional and surface photographic drawing of Figure 2 (pictured above) The cross section and the surface of the artificial brain film made using only silver silk, as shown in the cross-sectional view and the surface of the present invention below) has a smooth and uniform surface and cross-section while having a thickness of more than 300㎛.
In the case of the silk artificial brain dura, an example of the present invention, the elongation was greatly improved by 356.7%.
In addition, as can be seen in Figures 3a and 3b, the silk artificial brain dura, an example of the present invention has transparency to enable safe treatment during cerebral neurosurgery surgery.
In addition, as can be seen in Figure 4, the silk artificial brain dura, an example of the present invention has considerable flexibility, and as shown in Figure 5 maintains a suitable suture strength during surgery.
<Result 3> Results of Cytotoxicity Test
As a result of the cytotoxicity test of calcium chloride and silk contained in the silk artificial brain membrane of the present invention prepared in Example 1, as shown in Figs. 6a to 6b, irrespective of the concentration of the silk artificial brain dura extract, 24, 48 and 72 hours Almost 100% survival rate.
This result indicates that calcium chloride as well as silk contained in the silk artificial brain dura, which is an example of the present invention, do not exhibit cytotoxicity.
Claims (7)
The silk fibroin is 50.00 ~ 99.99% by weight, the salt is composed of 0.01 ~ 50.00% by weight,
Characterized in that it is made of a transparent membrane having a biocompatible and flexible and at the same time does not cause an inflammatory reaction,
Silk artificial film.
The salt is a silk artificial film, characterized in that any one of calcium chloride, sodium chloride, potassium chloride, sodium acetate.
Characterized in that for artificial brain dural or biological membrane,
Silk artificial film.
Pouring the mixed solution in a flat container and dried to prepare a silk artificial film made of a transparent film having a biocompatibility and does not cause an inflammatory reaction and at the same time flexible;
Method for producing silk artificial membranes for artificial brain dural and biological membranes.
The salt is characterized in that any one of calcium chloride, sodium chloride, potassium chloride, sodium acetate, method of producing a silk artificial membrane for artificial brain dural and biological membranes.
In the drying step, the mixed solution contained in the container is dried in a constant temperature room containing 20 ~ 80 ℃, 20 ~ 80% moisture, artificial membranes and artificial membranes for the production of silk artificial membranes.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20100133134A KR101322337B1 (en) | 2010-12-23 | 2010-12-23 | Silk artificial membrane for artificial dural membrane and biological membrane with excellent flexibility and solidity |
| PCT/KR2011/009826 WO2012086988A2 (en) | 2010-12-23 | 2011-12-20 | Artificial silk membrane having excellent flexibility and suturing ability and method of manufacturing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20100133134A KR101322337B1 (en) | 2010-12-23 | 2010-12-23 | Silk artificial membrane for artificial dural membrane and biological membrane with excellent flexibility and solidity |
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| Publication Number | Publication Date |
|---|---|
| KR20120071546A KR20120071546A (en) | 2012-07-03 |
| KR101322337B1 true KR101322337B1 (en) | 2013-10-25 |
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| KR20100133134A KR101322337B1 (en) | 2010-12-23 | 2010-12-23 | Silk artificial membrane for artificial dural membrane and biological membrane with excellent flexibility and solidity |
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| WO (1) | WO2012086988A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200051077A (en) | 2018-11-02 | 2020-05-13 | 오스젠 주식회사 | Artificial dura membrane and their manufacturing methods using Melt Electrospinning |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103341214B (en) * | 2013-07-08 | 2014-12-31 | 苏州大学 | Silk fibroin membrane and preparation method thereof |
| CN107441498A (en) * | 2017-06-12 | 2017-12-08 | 安徽省颍上县正泰电器有限责任公司 | A kind of preparation method of the carbon nano-tube modified composite stone wax powder powder material of nano-cellulose |
| CN108396425A (en) * | 2018-03-16 | 2018-08-14 | 青岛大学 | A kind of fibroin albumen/carbon nanotube serialization filament yarn and preparation method thereof |
| CN111572983B (en) * | 2020-04-26 | 2022-04-05 | 浙江天益塑业有限公司 | Preparation method of high-strength degradable paper-plastic composite bag |
| CN112813007A (en) * | 2021-02-23 | 2021-05-18 | 江苏科技大学 | Method for repairing biological material film by biological template method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20100121169A (en) * | 2009-05-08 | 2010-11-17 | 한림대학교 산학협력단 | Artificial eardrum using silk protein and method for fabricating the same |
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2010
- 2010-12-23 KR KR20100133134A patent/KR101322337B1/en active IP Right Grant
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- 2011-12-20 WO PCT/KR2011/009826 patent/WO2012086988A2/en active Application Filing
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20100121169A (en) * | 2009-05-08 | 2010-11-17 | 한림대학교 산학협력단 | Artificial eardrum using silk protein and method for fabricating the same |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200051077A (en) | 2018-11-02 | 2020-05-13 | 오스젠 주식회사 | Artificial dura membrane and their manufacturing methods using Melt Electrospinning |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012086988A3 (en) | 2012-09-27 |
| WO2012086988A9 (en) | 2012-11-15 |
| KR20120071546A (en) | 2012-07-03 |
| WO2012086988A2 (en) | 2012-06-28 |
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