KR102598611B1 - A method for manufacturing 3d transparent nanofibers for artificial retina and the 3d transparent nanofibers artificial retina thereof - Google Patents
A method for manufacturing 3d transparent nanofibers for artificial retina and the 3d transparent nanofibers artificial retina thereof Download PDFInfo
- Publication number
- KR102598611B1 KR102598611B1 KR1020210079042A KR20210079042A KR102598611B1 KR 102598611 B1 KR102598611 B1 KR 102598611B1 KR 1020210079042 A KR1020210079042 A KR 1020210079042A KR 20210079042 A KR20210079042 A KR 20210079042A KR 102598611 B1 KR102598611 B1 KR 102598611B1
- Authority
- KR
- South Korea
- Prior art keywords
- nanofibers
- transparent
- nanofiber
- manufacturing
- dimensional
- Prior art date
Links
- 239000002121 nanofiber Substances 0.000 title claims abstract description 97
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title abstract description 13
- 210000001525 retina Anatomy 0.000 title 2
- 239000000243 solution Substances 0.000 claims abstract description 25
- 239000007864 aqueous solution Substances 0.000 claims abstract description 19
- 238000009987 spinning Methods 0.000 claims abstract description 15
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 14
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 14
- 238000001035 drying Methods 0.000 claims abstract description 10
- 238000001523 electrospinning Methods 0.000 claims abstract description 10
- 210000004087 cornea Anatomy 0.000 claims description 18
- 239000000463 material Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 238000002054 transplantation Methods 0.000 description 10
- 102000011782 Keratins Human genes 0.000 description 8
- 108010076876 Keratins Proteins 0.000 description 8
- 239000004372 Polyvinyl alcohol Substances 0.000 description 8
- 229920002451 polyvinyl alcohol Polymers 0.000 description 8
- 239000000835 fiber Substances 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 239000013306 transparent fiber Substances 0.000 description 6
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 4
- 210000004209 hair Anatomy 0.000 description 4
- 229920005615 natural polymer Polymers 0.000 description 4
- 238000002834 transmittance Methods 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- 229920000297 Rayon Polymers 0.000 description 3
- 210000001691 amnion Anatomy 0.000 description 3
- 239000012620 biological material Substances 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 210000002268 wool Anatomy 0.000 description 3
- 229920001661 Chitosan Polymers 0.000 description 2
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 229940015043 glyoxal Drugs 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000004381 surface treatment Methods 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000002082 metal nanoparticle Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000002964 rayon Substances 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 239000012209 synthetic fiber Substances 0.000 description 1
- 239000012780 transparent material Substances 0.000 description 1
Classifications
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- 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
- 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
- A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L27/20—Polysaccharides
-
- 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
- A61L27/26—Mixtures of macromolecular compounds
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
-
- 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
- D04H1/70—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
- D04H1/72—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
- D04H1/728—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
-
- 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
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
-
- 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
- A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea
Landscapes
- Health & Medical Sciences (AREA)
- Transplantation (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Textile Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Mechanical Engineering (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Materials For Medical Uses (AREA)
Abstract
본 발명은 3차원의 투명한 나노섬유의 제조방법에 관한 것으로서, 구체적으로 생체조직과의 안정성 및 친화성이 개선된 3차원의 구조 나노섬유를 제조하되, 나노 사이즈로 방사된 나노 섬유를 투명하고 신축성 있게 제조하는 방법에 관한 것이다. 본 발명은 투명나노섬유 제조방법에 있어서, 나노섬유 방사원액을 준비하는 단계(S1); 나노섬유 방사원액을 전기 방사하여 나노섬유를 획득하는 단계(S2); 상기 나노섬유를 열처리하는 단계(S3); 상기 열처리한 나노섬유를 수소화붕소나트륨 수용액에 침지시키는 단계(S4); 상기 나노섬유를 건조시키는 단계(S5); 를 포함하는 3차원 구조의 투명 나노섬유의 제조방법이다.The present invention relates to a method for manufacturing three-dimensional transparent nanofibers. Specifically, the three-dimensional structural nanofibers with improved stability and affinity with biological tissue are manufactured, and the nanofibers spun in nano size are transparent and elastic. It's about how to manufacture it. The present invention provides a method for producing transparent nanofibers, comprising: preparing a nanofiber spinning solution (S1); Obtaining nanofibers by electrospinning the nanofiber spinning solution (S2); Heat treating the nanofibers (S3); Step (S4) of immersing the heat-treated nanofibers in an aqueous solution of sodium borohydride; Drying the nanofibers (S5); This is a method of manufacturing transparent nanofibers with a three-dimensional structure containing.
Description
본 발명은 3차원의 투명한 나노섬유 각막 제조방법 및 이 방법에 의해서 제조된 나노섬유 각막에 관한 것으로서, 구체적으로 생체조직과의 안정성 및 친화성이 개선된 3차원의 구조 나노섬유를 제조하되, 나노 사이즈로 방사된 나노 섬유를 투명하고 신축성 있게 제조하는 방법에 관한 것이다. The present invention relates to a method for manufacturing a three-dimensional transparent nanofiber cornea and a nanofiber cornea produced by this method. Specifically, the present invention relates to manufacturing a three-dimensional structured nanofiber with improved stability and affinity with biological tissue, This relates to a method of manufacturing transparent and elastic nanofibers spun to size.
통상 손상된 동물 또는 사람의 각막이식에 대해서 생체재료를 사용한다. 동물의 각막이식에는 말(horse)의 태반에서 얻은 양막(AM, Amnionic Membrane)을 사용하거나, 사람의 각막이식에는 타인의 기증각막을 기증받아서 각막을 이식한다. 다만, 사람의 경우 기증을 위해서 오랜 기간 대기하여야 하고, 각막의 거부반응 등의 부작용으로 호소하는 경우가 많다. 양막을 이용한 동물의 각막이식의 경우 그 두께가 일정하지 않기 때문에 각막의 결손된 부위에 이식할 경우 필요한 만큼의 두께를 정량화해서 이식하는데 한계가 있어 이식 후 각막이 울퉁불퉁 해지고 안 표면이 고르지 못해 이차적인 문제가 발생할 수 있다. 선행문헌의 종래기술에는 2차원 나노섬유에 관한 것이나, 이를 각막이식에 활용할 경우에 세포조직이 괴사하는 문제가 있다. Typically, biomaterials are used for corneal transplantation of damaged animals or humans. For animal cornea transplantation, amnionic membrane (AM) obtained from a horse's placenta is used, or for human cornea transplantation, a cornea donated by another person is donated. However, in the case of people, they have to wait a long time to donate and often complain of side effects such as corneal rejection. In the case of animal cornea transplantation using amniotic membrane, the thickness is not constant, so when transplanting to a defective part of the cornea, there are limitations in quantifying and transplanting the required thickness. After transplantation, the cornea becomes bumpy and the inner surface becomes uneven, resulting in secondary Problems may arise. The prior art in the prior literature relates to two-dimensional nanofibers, but there is a problem of cell tissue necrosis when used for corneal transplantation.
이에 본 발명의 발명자는 생체조직과의 안정성 및 친화성이 개선된 새로운 유형의 차세대 투명한 3차원 구조를 갖는 투명한 나노섬유를 간단하게 제조하기 위한 제조방법을 착안하게 되었다. Accordingly, the inventor of the present invention came up with a manufacturing method for simply manufacturing a new type of transparent nanofiber with a next-generation transparent three-dimensional structure with improved stability and affinity with biological tissue.
본 발명의 목적은 생체안정성 및 생체친화성이 뛰어난 3차원 구조의 투명하고 플랙서블한 나노섬유를 효율적으로 만드는 제조방법을 제공하는 것이다.The purpose of the present invention is to provide a manufacturing method for efficiently making transparent and flexible nanofibers with a three-dimensional structure having excellent biostability and biocompatibility.
상기와 같은 기술적 과제를 해결하기 위한 본 발명의 3차원 구조의 투명 나노섬유 각막 제조방법은, The method for manufacturing a transparent nanofiber cornea with a three-dimensional structure of the present invention to solve the above technical problems is,
나노섬유방사원액을 준비하는 단계(S1);Preparing a nanofiber spinning solution (S1);
나노섬유 방사원액을 전기 방사하여 나노섬유를 획득하는 단계(S2);Obtaining nanofibers by electrospinning the nanofiber spinning solution (S2);
상기 나노섬유를 열처리하는 단계(S3);Heat treating the nanofibers (S3);
상기 열처리한 나노섬유를 수소화붕소나트륨 수용액에 침지시키는 단계(S4);Step (S4) of immersing the heat-treated nanofibers in an aqueous solution of sodium borohydride;
상기 나노섬유를 건조시키는 단계(S5);Drying the nanofibers (S5);
를 포함한다. Includes.
한편, 상기 나노섬유 방사원액은, 천연의 고분자 수용액과 PVA를 블랜딩한 수용액인 것이다.Meanwhile, the nanofiber spinning solution is an aqueous solution blended with a natural polymer aqueous solution and PVA.
본 발명은 천연단백질과 블랜딩한 고분자 수용액을 전기방사하여 만들어진 투명나노섬유를 이용하여 인공각막을 이식할 수 있는데, 나노섬유를 기반으로 하는 투명섬유는 넓은 표면적, 표면처리의 다양성, 복합재료의 구성이 용이하여 기존 생체재료를 대체할 수 있다. The present invention can implant an artificial cornea using transparent nanofibers made by electrospinning an aqueous polymer solution blended with natural protein. Transparent fibers based on nanofibers have a large surface area, diversity of surface treatments, and composition of composite materials. This makes it easy to replace existing biomaterials.
기존에는 유기고분자나 여러 가지 복합재료, 금속 나노입자에 의해 투명한 소재를 여러가지 공정을 거쳐 만들어내는 방법에 비해, 본 발명은 전기방사법을 이용하여 나노섬유를 만든 뒤 수소화붕소나트륨 수용액에 침지하고 건조시키는 것만으로 3차원 구조의 투명한 나노섬유를 제조할 수 있어 신체 이식용 재료를 효율적이고 경제적으로 생산하는 것이 가능하게 된다. Compared to the existing method of producing transparent materials using organic polymers, various composite materials, or metal nanoparticles through various processes, the present invention uses electrospinning to create nanofibers, then immersing them in an aqueous solution of sodium borohydride and drying them. This alone makes it possible to manufacture transparent nanofibers with a three-dimensional structure, making it possible to efficiently and economically produce materials for body transplants.
2차원 구조로서 섬유의 내부공간이 충분하지 않아 이식된 재료에 의해 몸속의 조직이 괴사하여 각막 등의 적용에 문제가 있었으나, 본 발명에 따른 3차원 나노섬유는 생체 안정성과 친화성을 모두 충족하는 생체이식을 위한 투명한 각막 재료를 제공한다. As a two-dimensional structure, the internal space of the fiber is not sufficient, so the tissue in the body dies due to the implanted material, causing problems in application to the cornea, etc. However, the three-dimensional nanofiber according to the present invention satisfies both biostability and compatibility. Provides transparent corneal material for biological transplantation.
도 1은 본 발명의 일실시예에 따른 3차원 구조의 투명 나노섬유의 제조공정을 도시한 개략도이다.
도 2는 본 발명에 따른 3차원 구조의 투명 나노섬유의 외관사진이다.
도 3은 2차원 나노섬유(A)와 그의 단면(B), 3차원 투명 나노섬유(C)와 그의 단면(D)의 SEM 사진이다.
도 4는 본 발명에 따른 나노섬유 각막의 자외선 분광 광도계에 의해 측정된 투명도(A)와 인장강도(B)에 대한 그래프이다.
도 5는 3차원 투명 나노섬유의 각막이식 후 거부반응이 테스트 결과 거부반응이 없는 것이 확인된 사진이다.
Figure 1 is a schematic diagram showing the manufacturing process of transparent nanofibers with a three-dimensional structure according to an embodiment of the present invention.
Figure 2 is an external photograph of a transparent nanofiber with a three-dimensional structure according to the present invention.
Figure 3 is an SEM image of a two-dimensional nanofiber (A) and its cross section (B), and a three-dimensional transparent nanofiber (C) and its cross section (D).
Figure 4 is a graph of transparency (A) and tensile strength (B) measured by an ultraviolet spectrophotometer of the nanofiber cornea according to the present invention.
Figure 5 is a photograph showing that there was no rejection reaction after corneal transplantation of 3D transparent nanofibers.
본 발명의 3차원 구조의 투명나노섬유 인공각막 제조방법은, 크게 나노섬유를 준비하는 공정과 준비된 나노섬유를 수소화붕소나트륨 수용액에 침지하고 건조하는 공정으로 이루어진다. 즉, The method of manufacturing a transparent nanofiber artificial cornea with a three-dimensional structure of the present invention largely consists of a process of preparing nanofibers and a process of immersing the prepared nanofibers in an aqueous solution of sodium borohydride and drying them. in other words,
공정 1 : 나노섬유를 준비하는 공정 Process 1 : Process for preparing nanofibers
공정 2 : 준비된 나노섬유를 수소화붕소나트륨 수용액에 침지하고 건조하는 공정으로 이루어진다. Process 2 : It consists of immersing the prepared nanofibers in an aqueous solution of sodium borohydride and drying them.
상기 나노섬유를 준비하는 공정 1은 Process 1 of preparing the nanofibers is
다양한 방법으로 준비가 가능하되, 본 발명에서는 전기방사방법으로 나노섬유를 제조한다. It can be prepared in a variety of ways, but in the present invention, nanofibers are produced by electrospinning.
한편 전기방사에 사용되는 나노섬유 방사원액은 고분자 수용액과 폴리비닐알콜(Poly Vinyl Alcohol, PVA)용액을 혼합한 것을 준비한다.(S1) Meanwhile, the nanofiber spinning solution used for electrospinning is prepared by mixing a polymer aqueous solution and a polyvinyl alcohol (PVA) solution (S1).
상기 나노섬유 방사원액은 고분자 수용액을 이용하면 방사성이 뛰어나지만, 다만 분자량이 작은 재생케라틴의 경우, 방사성이 안좋아지므로 물에 쉽게 용해되면서 방사성을 좋게 하고 생체적합성이 뛰어난 PVA를 블랜딩할 수 있다. The nanofiber spinning solution has excellent spinnability when using an aqueous polymer solution, but in the case of regenerated keratin with a small molecular weight, spinnability is poor, so it can be blended with PVA, which easily dissolves in water, improves spinnability, and has excellent biocompatibility.
구체적으로, 본 발명의 나노섬유 방사원액은 천연의 고분자 수용액을 PVA와 블랜딩한 용액이며, 이외에도 고분자 수용액은 기타 공지의 방법으로 만들어질 수 있다. 즉, 상기 천연의 고분자 수용액은 셀룰로오스계, 단백질계를 포함한 천연 고분자 및 모든 종류의 키틴, 아세테이트, 레이온, 폴리에스테르, 나일론, 폴리에틸렌, 폴리비닐알콜을 포함한 합성섬유 및 아세테이트 레이온, 비스코스레이온을 포함한 재생 섬유로 이루어지는 군으로부터 1종 이상 선택된 것이다. Specifically, the nanofiber spinning solution of the present invention is a solution obtained by blending a natural aqueous polymer solution with PVA, and in addition, the aqueous polymer solution can be made by other known methods. In other words, the natural polymer aqueous solution includes natural polymers including cellulose and protein, all types of chitin, acetate, rayon, polyester, nylon, polyethylene, synthetic fibers including polyvinyl alcohol, and regenerated fibers including acetate rayon and viscose rayon. One or more types are selected from the group consisting of fibers.
단백질계 천연 고분자는 양모, 실크와 같은 천연 단백질 섬유, 머리카락, 동물의 털 또는 난간막으로부터 추출된 재생케라틴 수용액일 수 있다. 또한 키토산 용액은 키토산 저분자, 중분자, 그리고 고분자 수용액을 포함한다. The protein-based natural polymer may be an aqueous solution of regenerated keratin extracted from natural protein fibers such as wool and silk, hair, animal fur, or parapet membrane. Chitosan solutions also include low-molecular-weight, medium-molecular, and high-molecular chitosan aqueous solutions.
상기 방사원액을 전기방사하여 나노섬유를 획득하고(S2), 상기 나노섬유는 열처리에 의해서 물에 저항력, 즉 수불용성이 우수한 2차원 구조의 나노섬유로 변화된다.(S3) Nanofibers are obtained by electrospinning the spinning solution (S2), and the nanofibers are changed into two-dimensional nanofibers with excellent water resistance, that is, water insolubility, by heat treatment (S3).
다음 공정 2는, 상기 2차원 구조의 나노섬유를 3차원 구조의 투명나노섬유로 변환시키는 것이다. 이렇게 획득된 나노섬유는 물에 침지하는 것으로 투명한 나노섬유로 변화된다. 투명한 나노섬유는 각막이식에 유용하지만 본 발명은 상기 2차원 구조의 나노섬유를 물 대신 수소화붕소나트륨 수용액에 침지시킨다(S4). 물에 침지된 나노섬유는 투명한 나노섬유로 변화되며, 동시에 무기질인 수소화붕소나트륨에 침지된 후에 건조되는 과정(S5)에서 벌키(bulky)한 3차원 다공성 구조로 변화된다. 수소화붕소나트륨에서의 침지시간과 그 이후의 건조시간은 용도에 맞게 조절된다. 이와 같은 방법에 의해서 2차원 구조의 나노섬유가 상온에서도 용이하게 3차원 구조의 나노섬유로 변경될 수 있다. The next step 2 is to convert the two-dimensional nanofibers into three-dimensional transparent nanofibers. The nanofibers obtained in this way are changed into transparent nanofibers by immersing them in water. Transparent nanofibers are useful for corneal transplantation, but in the present invention, the two-dimensional nanofibers are immersed in an aqueous sodium borohydride solution instead of water (S4). Nanofibers immersed in water are changed into transparent nanofibers, and at the same time, they are changed into a bulky three-dimensional porous structure during the drying process (S5) after being immersed in the inorganic sodium borohydride. The soaking time in sodium borohydride and the subsequent drying time are adjusted according to the application. By this method, nanofibers with a two-dimensional structure can be easily changed into nanofibers with a three-dimensional structure even at room temperature.
3차원 다공성 구조의 투명한 나노섬유는 신체, 특히 각막의 표면에 접촉되어 각막의 세포와 친화성이 우수하게 되어 세포가 다공성 구조로 개재됨으로 인해서 신체와의 안정성 및 친화성이 좋다. Transparent nanofibers with a three-dimensional porous structure come into contact with the surface of the body, especially the cornea, and have excellent affinity with the cells of the cornea. As the cells are interposed in the porous structure, they have good stability and affinity with the body.
<실시예 1> 케라틴 나노섬유의 제조<Example 1> Preparation of keratin nanofibers
- 공정 1 : 물 100에 머리카락에서 추출한 재생케라틴 5중량부를 용해하여 재생케라틴 수용액을 획득한다. 본 발명에서는 머리카락으로부터 천연 단백질인 재생케라틴를 추출한 후 이를 물에 녹여 재생케라틴 수용액을 제조한다. 상기 양모는 폐기되는 양모를 활용하는 것도 가능하다. PVA 용액 10중량부를 상기 재생케라틴 수용액에 당량비 50:50으로 혼합한다.(S1)- Process 1: Obtain a regenerated keratin aqueous solution by dissolving 5 parts by weight of regenerated keratin extracted from hair in 100 parts of water. In the present invention, regenerated keratin, a natural protein, is extracted from hair and then dissolved in water to prepare a regenerated keratin aqueous solution. It is also possible to use discarded wool as the wool. 10 parts by weight of the PVA solution is mixed with the regenerated keratin aqueous solution at an equivalent ratio of 50:50 (S1).
- 상기 혼합액에 글리옥살 0.05중량부를 넣고 인산을 한방울 떨어뜨려 pH 3 의 방사원액을 만든 후에 0.36 mm 니들을 사용하고 syringe flow pump 전압을 20 kV로 하며, 방사원액 공급 속도 0.01 mL/min로 설정한 방사조건에 따라서 상기 방사원액을 전기방사하여 나노섬유를 제조한다.(S2) 상기 글리옥살과 인산은 산도 조절로 가교를 형성하여 PVA가 물에 불용되도록 하는 역할을 한다. - Add 0.05 parts by weight of glyoxal to the above mixed solution and add a drop of phosphoric acid to make a spinning solution of pH 3. Then, use a 0.36 mm needle, set the syringe flow pump voltage to 20 kV, and set the spinning solution supply speed to 0.01 mL/min. Nanofibers are manufactured by electrospinning the spinning solution according to spinning conditions. (S2) The glyoxal and phosphoric acid form crosslinks by adjusting the acidity, thereby making PVA insoluble in water.
- 상기 나노섬유를 120℃에서 5분 정도 열처리함으로써 수불용성의 생체 친화성 나노섬유를 획득한다. (S3) - Obtain water-insoluble, biocompatible nanofibers by heat-treating the nanofibers at 120°C for about 5 minutes. (S3)
- 공정 2 : 상기 나노섬유를 0.1M(몰)의 수소화붕소나트륨 수용액에 침지시킨다. (S4) 상기 침지된 나노섬유를 건조시킨다.(S5) 활용목적에 따라서 침지시간과 건조시간을 조절하여 투명한 3차원 구조의 나노섬유를 제조한다. 상기 수소화붕소나트륨 수용액의 농도는 0.001M ~ 1M 에서 가능하다. - Step 2: The nanofibers are immersed in 0.1M (mole) aqueous sodium borohydride solution. (S4) The immersed nanofibers are dried. (S5) The immersion time and drying time are adjusted according to the purpose of use to manufacture nanofibers with a transparent three-dimensional structure. The concentration of the sodium borohydride aqueous solution can be from 0.001M to 1M.
도 1은 본 발명의 일실시예에 따른 3차원 구조의 투명한 나노 섬유의 제조 공정을 나타낸 개략도이다.Figure 1 is a schematic diagram showing the manufacturing process of transparent nanofibers with a three-dimensional structure according to an embodiment of the present invention.
도 2는 2차원 나노섬유를 수소화붕소나트륨 수용액에 침지하여 건조한 투명한 3차원 나노섬유의 사진이다. Figure 2 is a photograph of a transparent three-dimensional nanofiber obtained by immersing the two-dimensional nanofiber in an aqueous solution of sodium borohydride and drying it.
2차원 나노섬유는 아직 투명섬유로 만들어지지 직전이며 바로 물에 침지시켜 투명섬유를 만들어 사용해도 무방하나 수소화붕소나트륨 수용액에 담그는 공정에서도 물에 노출이 되고 무기화합물에 의해 3차원 구조가 형성되어 원재료인 나노섬유를 바로 수소화붕소나트륨 수용액에 침지시켜 3차원 투명섬유를 제조한다. 3차원 투명 나노섬유의 겨우 두께를 일정하게 조걸하여 제조할 수 있다는 장점을 갖는다.2D nanofibers have not yet been made into transparent fibers, and can be used to make transparent fibers by immersing them in water. However, even in the process of immersing them in an aqueous solution of sodium borohydride, they are exposed to water and a three-dimensional structure is formed by inorganic compounds, making them raw materials. Phosphorus nanofibers are directly immersed in an aqueous solution of sodium borohydride to produce three-dimensional transparent fibers. It has the advantage of being able to manufacture three-dimensional transparent nanofibers by adjusting their thickness to a constant level.
도 3은 종래의 2차원 구조의 투명 나노섬유(A)와 그의 단면(B), 그리고 본 발명에 따른 3차원 구조의 투명 나노섬유(C)와 그의 단면(D)에 대한 SEM 사진이다. 2차원 투명 나노섬유의 조밀한 구조와 3차원 투명섬유의 엉성한 구조가 서로 상이하다. 즉 본 발명에 따른 3차원 구조의 나노섬유는 내부에 더 많은 다공성으로 인해서 부피감(bulky)을 확인할 수 있다. 3차원 구조의 투명 나노섬유의 경우 팽윤한 상태는 보이지만 섬유상이 살아있는 것을 확인할 수 있다. 이로써 본 발명의 3차원 구조의 투명 나노섬유가 인체의 세포조직에 접촉될 때 인체 조직의 세포가 다공성의 3차원 구조 나노섬유의 기공으로 침투하여 자연스럽게 일체로 되면서 생체와의 안정성 및 친화성이 좋게 된다. 특히, 각 섬유마다 성상의 차이가 있어 각각의 생분해, 투명함과 신축성 등 용도에 맞는 적용이 가능하다. Figure 3 is an SEM photograph of a conventional two-dimensional transparent nanofiber (A) and its cross section (B), and a three-dimensional transparent nanofiber according to the present invention (C) and its cross section (D). The dense structure of 2D transparent nanofibers and the loose structure of 3D transparent fibers are different from each other. In other words, the three-dimensional nanofiber according to the present invention can be confirmed to be bulky due to more porosity on the inside. In the case of transparent nanofibers with a three-dimensional structure, they appear swollen, but the fibers can be confirmed to be alive. As a result, when the transparent nanofiber with a three-dimensional structure of the present invention comes into contact with the cellular tissue of the human body, the cells of the human tissue penetrate into the pores of the porous three-dimensional nanofiber and naturally become integrated, improving stability and compatibility with the living body. do. In particular, each fiber has different properties, so it can be applied to suit each application, such as biodegradability, transparency, and elasticity.
도 4는 자외선 분광 광도계에 의해 측정된 각 나노섬유와 양막에 대한 각각의 투과도(A)와 인장강도(B)에 대한 그래프를 도시한 것으로서, 투과도는 빛이 통과하는 정도를 가리키는 것으로서, 75% 이상에서 양호한 투과도를 보이고, 80% 이상에서는 투과도가 현저하게 양호하게 된다. 또한 위 그래프를 통해서 본 발명에 따른 나노섬유는 양막에 비해 강한 신축성 및 인장강도를 가진 것을 확인 할 수 있다.Figure 4 shows a graph of the transmittance (A) and tensile strength (B) of each nanofiber and amniotic membrane measured by an ultraviolet spectrophotometer. The transmittance indicates the degree to which light passes, 75%. The above shows good transmittance, and above 80%, the transmittance becomes significantly good. In addition, through the above graph, it can be seen that the nanofiber according to the present invention has stronger elasticity and tensile strength than the amniotic membrane.
도 5는 본 발명에 따른 3차원 구조의 투명 나노섬유에 있어서 거부반응이 일어나는지를 살펴본 것으로서, 이식후 1주째(a, e, I), 2주째(b, f, j), 4주째(c, g, k), 그리고 8주째(d, h, l)에 거부반응이 없음이 확인되었다. Figure 5 shows whether rejection occurs in the three-dimensional transparent nanofiber according to the present invention, at 1 week (a, e, I), 2 weeks (b, f, j), and 4 weeks (c) after transplantation. , g, k), and at week 8 (d, h, l), it was confirmed that there was no rejection reaction.
본 발명은 천연단백질과 블랜딩한 고분자 수용액을 전기방사하여 만들어진 투명나노섬유를 이용하여 인공각막을 이식할 수 있는데, 나노섬유를 기반으로 하는 투명섬유는 넓은 표면적, 표면처리의 다양성, 복합재료의 구성이 용이하여 기존 생체재료를 대체할 수 있다. The present invention can implant an artificial cornea using transparent nanofibers made by electrospinning an aqueous polymer solution blended with natural protein. Transparent fibers based on nanofibers have a large surface area, diversity of surface treatments, and composition of composite materials. This makes it easy to replace existing biomaterials.
Claims (5)
나노섬유 방사원액을 준비하는 단계(S1);
나노섬유 방사원액을 전기 방사하여 나노섬유를 획득하는 단계(S2);
상기 나노섬유를 열처리하는 단계(S3);
상기 열처리한 나노섬유를 0.001M ~ 1M 농도의 수소화붕소나트륨 수용액에 침지시키는 단계(S4);
상기 나노섬유를 건조시키는 단계(S5);
를 포함하는 3차원 구조의 투명나노섬유 인공각막 제조방법.
In the method of manufacturing corneal material using transparent nanofibers,
Preparing a nanofiber spinning solution (S1);
Obtaining nanofibers by electrospinning the nanofiber spinning solution (S2);
Heat treating the nanofibers (S3);
Step (S4) of immersing the heat-treated nanofibers in an aqueous solution of sodium borohydride at a concentration of 0.001M to 1M;
Drying the nanofibers (S5);
A method of manufacturing a transparent nanofiber artificial cornea with a three-dimensional structure including.
A transparent nanofiber artificial cornea with a three-dimensional structure manufactured by the manufacturing method of claim 1.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020210079042A KR102598611B1 (en) | 2021-06-18 | 2021-06-18 | A method for manufacturing 3d transparent nanofibers for artificial retina and the 3d transparent nanofibers artificial retina thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020210079042A KR102598611B1 (en) | 2021-06-18 | 2021-06-18 | A method for manufacturing 3d transparent nanofibers for artificial retina and the 3d transparent nanofibers artificial retina thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20220169072A KR20220169072A (en) | 2022-12-27 |
KR102598611B1 true KR102598611B1 (en) | 2023-11-03 |
Family
ID=84567879
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020210079042A KR102598611B1 (en) | 2021-06-18 | 2021-06-18 | A method for manufacturing 3d transparent nanofibers for artificial retina and the 3d transparent nanofibers artificial retina thereof |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR102598611B1 (en) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101413095B1 (en) * | 2013-07-22 | 2014-07-02 | 주식회사 우리나노 | Method of manufacturing membranes comprising nano fiber with excellent transparency and flexibility |
US20170296703A1 (en) * | 2014-09-29 | 2017-10-19 | The Board Of Regents Of The University Of Nebraska | Nanofiber Structures and Methods of Synthesis and Use Thereof |
KR101843347B1 (en) | 2016-11-28 | 2018-03-29 | 전북대학교산학협력단 | Nano-fiber form for treatment of aneurysm and manufacturing method of the same |
US20200164107A1 (en) | 2017-06-09 | 2020-05-28 | Board Of Regents Of The University Of Nebraska | Nanofiber structures and methods of use thereof |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP7005408B2 (en) * | 2018-03-28 | 2022-02-10 | 国立大学法人信州大学 | Artificial cornea and method for manufacturing artificial cornea |
-
2021
- 2021-06-18 KR KR1020210079042A patent/KR102598611B1/en active IP Right Grant
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101413095B1 (en) * | 2013-07-22 | 2014-07-02 | 주식회사 우리나노 | Method of manufacturing membranes comprising nano fiber with excellent transparency and flexibility |
US20170296703A1 (en) * | 2014-09-29 | 2017-10-19 | The Board Of Regents Of The University Of Nebraska | Nanofiber Structures and Methods of Synthesis and Use Thereof |
KR101843347B1 (en) | 2016-11-28 | 2018-03-29 | 전북대학교산학협력단 | Nano-fiber form for treatment of aneurysm and manufacturing method of the same |
US20200164107A1 (en) | 2017-06-09 | 2020-05-28 | Board Of Regents Of The University Of Nebraska | Nanofiber structures and methods of use thereof |
Non-Patent Citations (1)
Title |
---|
Jawun Choi et al. "Keratin/poly (vinyl alcohol) blended nanofibers with high optical transmittance." Polymer (2015), Vol. 58, pp. 146-152 |
Also Published As
Publication number | Publication date |
---|---|
KR20220169072A (en) | 2022-12-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Srivastava et al. | Enhanced potential of biomimetic, silver nanoparticles functionalized Antheraea mylitta (tasar) silk fibroin nanofibrous mats for skin tissue engineering | |
CN106310349A (en) | Regenerated fibroin protein gel mask | |
ITVR20010098A1 (en) | PROCEDURE FOR OBTAINING SILK FIBROIN HYDROGELS. | |
CN103341209A (en) | Silk fibroin nanofiber membrane and preparation method thereof | |
CA2788221C (en) | Chitosan fiber | |
KR20070118730A (en) | Wound dressing materials with excellent ability to moisturized skin and method of manufacturing the same | |
US8445742B2 (en) | Wound dressing and process for producing the same and use thereof | |
Bao et al. | Agar/collagen membrane as skin dressing for wounds | |
KR101510589B1 (en) | Antimicrobial PTFE nanofibrous GBR membrane and preparation method thereof | |
KR20110040389A (en) | Preparation method of silk/hydroxyapatite hybrid nanofiber scaffold for bone regeneration | |
Hassabo et al. | Natural polymers in medical textiles | |
Syed et al. | Current issues and potential solutions for the electrospinning of major polysaccharides and proteins: A review | |
KR102598611B1 (en) | A method for manufacturing 3d transparent nanofibers for artificial retina and the 3d transparent nanofibers artificial retina thereof | |
Mejía et al. | Poly (vinyl alcohol)/Silk Fibroin/Ag NPs composite nanofibers for bone tissue engineering | |
Das et al. | Silk fiber composites in biomedical applications | |
Esfahani et al. | Effect of ha nanoparticles on adsorption of vitamin d3 on super-hydrophobic pa6 nanofibrous scaffold | |
Abdu et al. | Selected natural fibers and their electrospinning | |
KR20210112960A (en) | medical nano mat comprising silk and ceramic fiber | |
CN113981610A (en) | Antibacterial keratin nanofiber membrane and preparation method thereof | |
KR20170047531A (en) | Alginate Fiber For Maskpack Having Excellent Gelation Property And Process Of Producing Thereof | |
Teixeira et al. | Optimization of the crosslinking process with glutaraldehyde vapor in PVA based electrospun membranes to wound dressings applications | |
John et al. | Silk: An Explorable Biopolymer in the Biomedical Arena | |
RU2714671C1 (en) | Three-dimensional porous composite material and a method for production thereof | |
KR101186004B1 (en) | Method of fabrication of silk nanofibrous membrane with a controllable biodegradability and an implant biomaterial prepared by using the method | |
Azam et al. | Preparation and characterization of alginate hydrogel fibers reinforced by cotton for biomedical applications. Polymers. 2022; 14: 4707 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant |