KR101555513B1 - The polytetrafluoroethylene nanofibrous membrane for Guided bone regeneration and manufacturing method of the same - Google Patents

The polytetrafluoroethylene nanofibrous membrane for Guided bone regeneration and manufacturing method of the same Download PDF

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KR101555513B1
KR101555513B1 KR1020140002066A KR20140002066A KR101555513B1 KR 101555513 B1 KR101555513 B1 KR 101555513B1 KR 1020140002066 A KR1020140002066 A KR 1020140002066A KR 20140002066 A KR20140002066 A KR 20140002066A KR 101555513 B1 KR101555513 B1 KR 101555513B1
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peo
ptfe
polytetrafluoroethylene
nanofiber
degradable
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KR20150082757A (en
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김영진
박진영
이정희
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대구가톨릭대학교산학협력단
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Abstract

본 발명은 폴리테트라플루오르에틸렌을 포함하는 골유도재생술용 비분해성 나노섬유 멤브레인 및 이의 제조방법에 관한 것으로서, 생체적합성, 기계적 강도, 유연성, 다공성 및 낮은 염증반응성을 갖는 비분해성 나노섬유 멤브레인을 제공하는 뛰어난 효과가 있다.The present invention relates to a non-degradable nanofiber membrane for bone induction regeneration comprising polytetrafluoroethylene and a method for producing the same, and to provide a non-degradable nanofiber membrane having biocompatibility, mechanical strength, flexibility, porosity and low inflammation reactivity It has excellent effect.

Description

골유도재생술용 폴리테트라플루오르에틸렌 나노섬유 멤브레인 및 그 제조방법{The polytetrafluoroethylene nanofibrous membrane for Guided bone regeneration and manufacturing method of the same}TECHNICAL FIELD The present invention relates to a polytetrafluoroethylene nanofiber membrane for bone induction regeneration and a method of manufacturing the same.

본 발명은 폴리테트라플루오르에틸렌 비분해성 나노섬유 멤브레인에 관한 것으로, 더욱 상세하게는 비분해성 멤브레인에 사용되는 폴리테트라플루오르에틸렌을 나노섬유의 형태로 제조함으로써 우수한 생체적합성과 기계적 강도, 유연성 및 균일한 다공성이 부여된 것이 특징인 나노섬유 멤브레인과 그 제조방법에 관한 것이다.The present invention relates to a polytetrafluoroethylene non-decomposable nanofiber membrane, and more particularly, to a polytetrafluoroethylene non-decomposable nanofiber membrane which is excellent in biocompatibility, mechanical strength, flexibility and uniform porosity The present invention relates to a nanofiber membrane and a method for producing the nanofiber membrane.

최근 임플란트의 보급이 대중화되면서 임플란트에 대한 관심이 증대되고 있다. 그로 인해 치과분야에서 임플란트의 성공률을 높이고자 하는 연구가 진행 중이다. 임플란트의 성공률을 높이기 위해서는 우선적으로 임플란트가 이식될 뼈의 강도가 중요하다. 하지만 손상된 부위에서 골조직의 재생속도보다 연조직의 재생 및 침입속도가 빠르기 때문에 충분한 골조직의 강도 확보가 어렵다는 문제점이 있다. 이러한 문제점을 해결하기 위해 연조직의 침입을 막아 충분한 골조직의 재생이 가능한 공간을 확보해 주는 골유도재생술(Guided bone regeneration)이 이용되고 있다. 골유도재생술에는 골조직재생의 촉진과 더불어 연조직의 침입을 막기 위해 공간을 확보할 수 있는 우수한 강도의 멤브레인이 핵심이다.Recently, as the spread of implants becomes popular, interest in implants is increasing. Research is underway to increase the success rate of implants in the dental field. In order to increase the success rate of the implant, the strength of the bone to which the implant is implanted is important. However, there is a problem in that it is difficult to obtain sufficient bone tissue strength because the regeneration and invasion speed of the soft tissue is faster than the regeneration speed of the bone tissue at the damaged site. Guided bone regeneration has been used to solve this problem by securing sufficient space for regeneration of bone tissue by preventing invasion of soft tissues. In bone induction regeneration, it is essential to promote the regeneration of bone tissue and to have a membrane of excellent strength that can secure space to prevent invasion of soft tissues.

폴리테트라플루오르에틸렌(Polytetrafluoroethylene)은 유기고분자 계열에 속하는 비가연성 불소 수지로서 약자인 PTFE 또는 미국 듀퐁(Dupont)사의 상품명인 테프론(Teflon)으로 많이 알려져 있다. 대부분의 화학약품에 대해 내화학성이 있고 마찰계수가 극히 낮으며, －270∼260℃의 온도범위에서 물리적 성질을 유지한다. 이러한 성질 때문에 사람의 생체 조직 또는 생체 물질과 장시간 접촉해도 악영향을 미치지 않는 생체재료로 유용하다.Polytetrafluoroethylene is known as PTFE which is abbreviation of non-flammable fluorocarbon resin belonging to organic polymer series or Teflon which is a trade name of Dupont, USA. It is chemically resistant to most chemicals, has an extremely low coefficient of friction, and maintains its physical properties in the temperature range of -270 to 260 ° C. Such properties are useful as biomaterials that do not adversely affect long-term contact with living tissue or biomaterial of a person.

전기방사법(electrospinning)을 이용하여 제조한 나노섬유형 소재는 높은 비 표면적을 지니고 있으며 세포외기질과 유사한 구조로 인하여 단백질 흡착 및 초기 세포 부착반응에 탁월하다고 알려져 있다. 전기방사법으로 폴리테트라플루오르에틸렌 나노섬유를 제조하기 위해서 폴리에틸렌옥사이드(Polyethyleneoxide; PEO), 폴리비닐피리딘(polyvinylpyridine; PVP), 젤라틴(Gelatin) 등의 전기방사가 가능한 유기 고분자와 혼합하여 사용해야 한다. 전기방사된 나노섬유는 열처리를 통해 폴리테트라플루오르에틸렌을 제외한 고분자를 제거하는 과정을 거친다. 유기 고분자와 폴리테트라플루오르에틸렌의 혼합 후 전기방사 능력 유지 및 열처리를 통한 제거의 가능성을 고려하여 폴리에틸렌옥사이드를 이용하여 전기방사 및 멤브레인을 제조한다. 폴리테트라플루오르에틸렌 멤브레인 제조에 있어 종래에 사용하지 않던 전기방사법으로 나노섬유 차폐막을 제조하면 높은 비 표면적을 부여하면서 폴리테트라플루오르에틸렌이 가지는 고유한 물성을 유지하여 우수한 차폐막의 제조가 가능하다고 사료된다.
The nanofiber-type material prepared by electrospinning has a high specific surface area and is known to be superior to protein adsorption and early cell adhesion reaction due to a structure similar to extracellular matrix. In order to prepare polytetrafluoroethylene nanofibers by electrospinning, they should be mixed with electrospunable organic polymers such as polyethylene oxide (PEO), polyvinylpyridine (PVP), and gelatin. The electrospun nanofibers are subjected to heat treatment to remove the polymer except polytetrafluoroethylene. Electrospinning and membrane fabrication using polyethylene oxide is carried out in consideration of the possibilities of retention of electrospinning ability after mixing of organic polymer and polytetrafluoroethylene and removal by heat treatment. It is believed that the fabrication of nanofiber shielding membranes by electrospinning, which has not been used in the prior art in the production of polytetrafluoroethylene membranes, permits the production of excellent shielding membranes by maintaining the inherent physical properties of polytetrafluoroethylene while imparting a high specific surface area.

차폐막 관련 기술로는 폴리카프로락톤 및 생체활성 유리를 포함하는 골유도재생용 차폐막에 대하여 대한민국 등록특허 제10-0738476호에 개시된 바 있고, 선택적 투과성 및 골 점착성을 가지는 다공성 골유도재생막 및 그 제조방법에 대하여 등록특허 제10-1016372호에 개시된 바 있다. 콜라겐과 수화젤이 결합된 다중층 복합 차폐막에 대하여는 등록특허 제10-1260757호에 개시된 바 있고, 폴리(L-락티드)와 폴리N-아세틸 글리코사미노글리칸 또는 폴리(D-글루코사민)을 혼합하여 형성된 골재생용 차단막에 대하여 등록특허 제10-1221339호에 개시된 바 있다.As a shielding film related technology, there is disclosed a shielding film for bone induction / regeneration including polycaprolactone and bioactive glass disclosed in Korean Patent Registration No. 10-0738476, and a porous bone induction regeneration membrane having selective permeability and bone adhesion, For example, in Japanese Patent Application Laid-Open No. 10-1016372. For the multilayer composite shielding film in which collagen and hydrated gel are combined, it is disclosed in Korean Patent No. 10-1260757, wherein poly (L-lactide) and poly N- acetylglycosaminoglycan or poly (D-glucosamine) And an aggregate biomembrane formed by mixing is disclosed in Korean Patent No. 10-1221339.

그러나 상기 특허문헌 어디에도 전기방사법을 이용하여 폴리테트라플루오르에틸렌 나노섬유를 제조하는 방법에 대하여는 전혀 개시되거나 암시된 바 없다.However, none of the above patent publications discloses or suggests any method for producing polytetrafluoroethylene nanofibers using electrospinning.

따라서 본 발명의 목적은 전기방사법을 이용하여 생체적합성, 유연성, 다공성 및 인체 내 불활성을 갖는 비분해성 폴리테트라플루오르에틸렌 골유도재생술용 나노섬유 멤브레인의 제조방법을 제공하는 데 있다.Accordingly, an object of the present invention is to provide a method for producing a nanofiber membrane for non-degradable polytetrafluoroethylene bone induction regeneration having biocompatibility, flexibility, porosity and in-vivo inertness by using electrospinning.

본 발명의 다른 목적은 상기 방법에 따라 제조된 비분해성 폴리테트라플루오르에틸렌 나노섬유 멤브레인을 제공하는 데 있다.Another object of the present invention is to provide a non-degradable polytetrafluoroethylene nanofiber membrane prepared according to the above method.

본 발명의 상기 목적은 증류수에 폴리에틸렌옥사이드(Polyethyleneoxide; PEO)를 용해시켜 폴리에틸렌옥사이드 수용액을 형성하는 단계와; 상기 단계에서 얻은 폴리에틸렌옥사이드 수용액에 폴리테트라플루오르에틸렌 Polytetrafluoroethylene(PTFE) 수분산액을 물에 혼합하여 PEO/PTFE 혼합 용액을 제조하는 단계와; 상기 단계에서 얻은 PEO/PTFE 혼합 용액의 고형분을 용매인 물에 대하여 20wt.%로 고정하고 24시간 교반하여 PEO/PTFE 고분자 혼합 교반용액을 제조하는 단계와; 상기 단계에서 얻은 고분자 혼합 교반용액을 전기방사하여 비분해성 나노섬유를 수득하는 단계와; 상기 단계에서 얻은 비분해성 나노섬유를 300℃에서 승온조건으로 열처리하여 폴리테트라플루오르에틸렌(PTFE)만을 남기면서 나노섬유 형태를 유지하는 단계로 이루어지는 것을 특징으로 하고; 상기 단계에서 얻은 비분해성 나노섬유 멤브레인의 골 조직재생 효과를 평가하는 단계를 통하여 달성하였다.The above object of the present invention is achieved by a method for producing a polyethylene oxide solution, comprising the steps of: dissolving polyethylene oxide (PEO) in distilled water to form a polyethylene oxide aqueous solution; Mixing a polytetrafluoroethylene polytetrafluoroethylene (PTFE) aqueous dispersion solution with water in the polyethylene oxide aqueous solution obtained in the above step to prepare a PEO / PTFE mixed solution; The solid content of the PEO / PTFE mixed solution obtained in the above step is fixed at 20 wt.% With respect to water as a solvent and stirred for 24 hours to prepare a PEO / PTFE polymer mixed solution. Dissolving the polymer mixed solution obtained in the above step in an electrospun to obtain non-degradable nanofibers; Treating the non-degradable nanofibers obtained in the above step at a temperature of 300 ° C under a temperature elevated condition to maintain the nanofiber shape while leaving only polytetrafluoroethylene (PTFE); And evaluating the bone tissue regeneration effect of the non-degradable nanofiber membrane obtained in the above step.

본 발명은 생체적합성, 유연성, 다공성 및 인체 내 불활성을 갖는 골유도재생술용 폴리테트라플루오르에틸렌 나노섬유 멤브레인 및 그 제조방법을 제공하는 뛰어난 효과가 있다.The present invention provides a polytetrafluoroethylene nanofiber membrane for bone induction regeneration having biocompatibility, flexibility, porosity and in-vivo inertness and a method for producing the same.

도 1은 본 발명에 따른 (a) 비교예 1의 PEO/PTFE 혼합 나노섬유 멤브레인, (b) 제조예 1의 PEO/PTFE 혼합 나노섬유 멤브레인, (c) 제조예 2의 PEO/PTFE 혼합 나노섬유 멤브레인, (d) 제조예 3의 PEO/PTFE 혼합 나노섬유 멤브레인의 SEM 촬영 사진도이다.
도 2는 본 발명에 따른 비분해성 나노섬유 멤브레인 (a)-(d)의 EDX분석 결과를 나타낸 그래프이다.
도 3은 본 발명에 따른 비분해성 나노섬유 멤브레인 (a)-(d)의 ATR-FTIR측정 결과를 나타낸 그래프이다.
도 4는 본 발명에 따른 비분해성 나노섬유 멤브레인 (a)-(d)의 TGA분석 결과를 나타낸 그래프이다.
도 5는 본 발명에 따른 비분해성 나노섬유 멤브레인 (a)-(d)의 XRD분석 결과를 나타낸 그래프이다.
도 6은 본 발명에 따른 비분해성 나노섬유 멤브레인 TCP 및 (b)-(d)의 세포의 증식력 및 부착력 측정 결과를 나타낸 그래프이다.
도 7은 본 발명에 따른 비분해성 나노섬유 멤브레인 (b)-(d)의 세포의 증식력 및 부착력을 나타낸 SEM 촬영 사진도이다.
도 8은 본 발명에 따른 비분해성 나노섬유 멤브레인 TCP 및 (b)-(d)의 세포의 분화력 측정 결과를 나타낸 그래프이다.
도 9는 본 발명에 따른 비분해성 나노섬유 멤브레인 TCP 및 (b)-(d)의 세포의 골형성력 측정 결과를 나타낸 그래프이다.
도 10은 본 발명에 따른 비분해성 나노섬유 멤브레인 TCP 및 (b)-(d)의 염증활성 측정 결과를 나타낸 그래프이다.
이하, 본 발명의 구체적인 내용을 도면과 실시예에 의거 더욱 상세히 설명한다.1 shows the PEO / PTFE mixed nanofiber membrane of Comparative Example 1, (b) the PEO / PTFE mixed nanofiber membrane of Preparation Example 1, (c) the PEO / PTFE mixed nanofiber membrane of Preparation Example 2, (D) SEM photographs of the PEO / PTFE mixed nanofiber membrane of Production Example 3.
2 is a graph showing the results of EDX analysis of non-degradable nanofiber membranes (a) - (d) according to the present invention.
3 is a graph showing the results of ATR-FTIR measurement of non-degradable nanofiber membranes (a) - (d) according to the present invention.
4 is a graph showing the results of TGA analysis of non-degradable nanofiber membranes (a) - (d) according to the present invention.
5 is a graph showing the XRD analysis results of the non-degradable nanofiber membranes (a) - (d) according to the present invention.
FIG. 6 is a graph showing the measurement results of the proliferation and adhesion of the non-degradable nanofiber membrane TCP and (b) - (d) according to the present invention.
FIG. 7 is a SEM photograph showing the proliferation and adhesion of non-degradable nanofiber membranes (b) - (d) according to the present invention.
FIG. 8 is a graph showing the results of measuring the partitioning force of the non-degradable nanofiber membrane TCP and (b) - (d) according to the present invention.
FIG. 9 is a graph showing the results of measuring the bone formation capacity of non-degradable nanofiber membrane TCP and (b) - (d) cells according to the present invention.
10 is a graph showing the results of measuring the inflammatory activity of the non-degradable nanofiber membrane TCP and (b) - (d) according to the present invention.
Hereinafter, the present invention will be described in more detail with reference to the drawings and examples.

본 발명은 폴리테트라플루오르에틸렌(polytetrafluoroetylene : PTFE) 나노섬유(nanofibrous) 멤브레인(membrane)을 제공한다. The present invention provides a polytetrafluoroethylene (PTFE) nanofibrous membrane.

본 발명에 따르면 상기 폴리테트라플루오르에틸렌은 폴리테트라플루오르에틸렌이 분산된 용액, 폴리테트라플루오르에틸렌 파우더(powder), 폴리테트라플루오르에틸렌 비드(bead), 폴리테트라플루오르에틸렌 그래뉼(granule) 중 선택되는 1종 또는 2종이다. According to the present invention, the polytetrafluoroethylene may be one selected from the group consisting of polytetrafluoroethylene-dispersed solution, polytetrafluoroethylene powder, polytetrafluoroethylene bead and polytetrafluoroethylene granule Or two.

본 발명에 따르면 폴리에틸렌옥사이드(PEO) 용해를 목적으로 사용할 수 있는 용매는 염화 메틸렌 (methylene chloride), 클로로포름 (chloroform), 아세톤 (acetone), 아니솔 (anisole), 아세트산 에틸 (ethyl acetate), 아세트산 메틸 (methyl acetate), N-메틸-2-피롤리돈 (N-methyl-2-pyrrolidone), 헥사플루오로이소프로판올 (hexafluoroisopropanol), 테트라하이드로퓨란 (tetrahydrofuran), 디메틸설폭사이드 (dimethylsulfoxide), 2-피롤리돈 (2-pyrollidone), 구연산 트리에틸 (triethyl citrate), 유산 에틸 (ethyl lactate), 프로필렌 카보네이트 (propylene carbonate), 벤질 알코올 (benzyl alcohol), 벤조산 벤질 (benzyl benzoate), 미글리올810 (Miglyol810), 이소프로판올 (isopropanol), 에탄올 (ethanol), 초임계 이산화탄소 (super critical carbon dioxide), 아세토니트릴 (acetonitrile) 및 물로 이루어진 군으로부터 선택되는 1종 또는 2종 이상의 혼합 용매이다. According to the present invention, solvents which can be used for the purpose of dissolving polyethylene oxide (PEO) are methylene chloride, chloroform, acetone, anisole, ethyl acetate, methyl acetate for example, methyl acetate, N-methyl-2-pyrrolidone, hexafluoroisopropanol, tetrahydrofuran, dimethylsulfoxide, 2- But are not limited to, 2-pyrollidone, triethyl citrate, ethyl lactate, propylene carbonate, benzyl alcohol, benzyl benzoate, Miglyol 810, , Isopropanol, ethanol, supercritical carbon dioxide, acetonitrile, and water for the mixing of one or more selected from the group consisting of water, A.

본 명세서에 달리 정의하지 않는 한, 사용된 모든 기술 및 과학 용어는 당업계에 통상의 기술자가 통상적으로 이해하는 바와 같은 의미를 가진다. 본 명세서에 포함되는 용어를 포함하는 다양한 과학적 사전이 잘 알려져 있고, 당업계에서 이용가능하다. 비록 본 명세서에 설명된 것과 유사 또는 등가인 임의의 방법 및 물질이 본 발명의 실시예 또는 실험예에 사용되는 것으로 발견되나, 몇몇 방법 및 물질이 설명되어 있다. 당업자가 사용하는 맥락에 따라, 다양하게 사용될 수 있기 때문에, 특정 방법학, 프로토콜 및 시약으로 본 발명을 제한하는 것으로 이해되어서는 안 된다.Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Various scientific dictionaries, including the terms contained herein, are well known and available in the art. Although any methods and materials similar or equivalent to those described herein have been found to be used in the embodiments or examples of the invention, some methods and materials have been described. Should not be construed as limiting the invention to the particular methodology, protocols and reagents, as they may be used in various ways in accordance with the context in which those skilled in the art use them.

본 명세서에서 사용되는 바와 같이, 단수형은 문맥이 명확하게 달리 지시하지 않으면 복수의 대상을 포함한다. 본 명세서에서 사용되는 바와 같이, 달리 언급되지 않는 한, "또는"은 "및/또는"을 의미한다. 더욱이, 용어 "포함하는" 뿐만 아니라, 다른 형태, 예를 들어, "가지는", “이루어지는” 및 "구성되는"는 제한적이지 않다. As used herein, the singular forms include plural objects unless the context clearly dictates otherwise. As used herein, unless otherwise stated, "or" means "and / or ". Furthermore, it is to be understood that other forms, such as " having ", " consisting ", and "consisting"

이하, 본 발명의 구체적인 내용을 바람직한 실시예 및 실험예를 통하여 상세히 설명하나, 하기 실시예 및 실험예에 의해 본 발명의 권리범위가 한정되는 것은 아니다.
Hereinafter, the present invention will be described in detail with reference to preferred embodiments and experimental examples. However, the scope of the present invention is not limited by the following examples and experimental examples.

실시예Example 1: 본 발명  1: invention 폴리테트라플루오르에틸렌Polytetrafluoroethylene 나노섬유  Nanofiber 멤브레인Membrane 제조 Produce

분자량이 600,000인 폴리에틸렌옥사이드(PEO, Sigma-Aldrich Co.) 0.5 g을 물 7.5 mL에 용해하여 6.7wt.% PEO용액을 제조하였다. 그리고 물에 고형분 60wt.%로 분산되어 있는 폴리테트라플루오르에틸렌(PTFE, Sigma-Aldrich Co.) 분산액 2.5 mL를 상기 PEO용액과 혼합하여 PEO/PTFE 혼합용액을 제조하였다. 최종적으로 PEO와 PTFE의 고형분을 용매인 물에 대해서 20wt.%로 고정하였으며, 상기 PEO와 PTFE의 혼합비는 1:2 ~ 1:5(w/w)이며 가장 바람직하기는 1:3(w/w)이다.0.5 g of polyethylene oxide (PEO, Sigma-Aldrich Co.) having a molecular weight of 600,000 was dissolved in 7.5 mL of water to prepare a 6.7 wt.% PEO solution. Then, 2.5 mL of a dispersion of polytetrafluoroethylene (PTFE, Sigma-Aldrich Co.) having a solid content of 60 wt.% Dispersed in water was mixed with the PEO solution to prepare a PEO / PTFE mixed solution. Finally, the solid content of PEO and PTFE was fixed at 20 wt.% With respect to water as a solvent. The mixing ratio of PEO to PTFE was 1: 2 to 1: 5 (w / w) w).

상기 제조된 고분자 용액에 상기 실시예 1에 따라 제조된 본 발명 PEO/PTFE 혼합용액을 24시간 상온에서 교반시켜 고분자 PEO/PTFE 혼합용액을 제조한 다음 전기방사 및 열처리함으로써 본 발명 비분해성 나노섬유 멤브레인을 제조하였다. 전기방사는 전압 14kV, 방사거리 15 cm, 용액 방사 속도는 1mL/h로 고정하여 수행하였다. 열처리는 20℃/h의 승온조건으로 수행하며, 200℃, 300℃, 330℃로 각각 처리하며 온도에 도달하면 10분간 추가적으로 열처리를 수행하였다 The PEO / PTFE mixed solution prepared in Example 1 was stirred at room temperature for 24 hours to prepare a polymeric PEO / PTFE mixed solution. Then, the polymer solution was subjected to electrospinning and heat treatment to obtain a non-degradable nanofiber membrane . The electrospinning was carried out at a voltage of 14 kV, a spinning distance of 15 cm, and a solution spinning rate of 1 mL / h. The heat treatment was performed at a temperature elevation rate of 20 ° C / h, and treated at 200 ° C, 300 ° C, and 330 ° C, respectively. When the temperature was reached, heat treatment was further performed for 10 minutes

제조예Manufacturing example 1: 본 발명  1: invention PEOPEO // PTFEPTFE 혼합 나노섬유를 200℃에서 열처리한  Mixed nanofibers were heat treated at 200 ° C 멤브레인Membrane

물에 PEO와 PTFE의 무게비 1:3(w/w)로 혼합하여 제조한 용액을 24시간 교반시켰다. 전기방사는 전압 14kV, 방사거리 15cm, 용액 방사 속도는 1mL/h로 고정하여 수행하였다. 상기 제조된 나노섬유 멤브레인을 상온에서 20℃/h의 승온조건으로 200℃까지 열처리하며, 200℃에 도달하면 10분간 200℃를 유지하였다.       The solution prepared by mixing PEO and PTFE at a weight ratio of 1: 3 (w / w) in water was stirred for 24 hours. The electrospinning was performed at a voltage of 14 kV, a spinning distance of 15 cm, and a solution spinning rate of 1 mL / h. The prepared nanofiber membrane was heat-treated at room temperature to 200 ° C at a temperature elevation rate of 20 ° C / h. When the temperature reached 200 ° C, the temperature was maintained at 200 ° C for 10 minutes.

제조예Manufacturing example 2: 본 발명  2: invention PEOPEO // PTFEPTFE 혼합 나노섬유를 300℃에서 열처리한  The mixed nanofibers were heat treated at 300 ° C 멤브레인Membrane

본 발명 나노섬유 멤브레인의 열처리를 200℃에서 20℃/h의 승온조건으로 300℃까지 열처리하며, 300℃에 도달하면 10분간 300℃를 유지하는 것을 제외하고는, 상기 제조예 1과 동일한 방법으로 나노섬유 멤브레인을 제조하였다.       The heat treatment of the nanofiber membrane of the present invention was carried out in the same manner as in Production Example 1, except that the heat treatment was performed at 200 ° C under a temperature elevation condition of 20 ° C / h up to 300 ° C and when the temperature reached 300 ° C, 300 ° C was maintained for 10 minutes Nanofiber membranes were prepared.

제조예Manufacturing example 3: 본 발명  3: invention PEOPEO // PTFEPTFE 혼합 나노섬유를 330℃에서 열처리한  The mixed nanofibers were heat-treated at 330 ° C 멤브레인Membrane

본 발명 나노섬유 멤브레인의 열처리를 300℃에서 20℃/h의 승온조건으로 330℃까지 열처리하며, 330℃에 도달하면 10분간 330℃를 유지하는 것을 제외하고는, 상기 제조예 1 또는 2와 동일한 방법으로 나노섬유 멤브레인을 제조하였다.The heat treatment of the nanofiber membrane of the present invention was performed at 300 ° C under a temperature elevation condition of 20 ° C / h to 330 ° C, and when 330 ° C was reached, 330 ° C was maintained for 10 minutes, A nanofiber membrane was prepared.

비교예Comparative Example 1: 본 발명  1: invention PEOPEO // PTFEPTFE 혼합 나노섬유  Mixed nanofiber 멤브레인Membrane

열처리를 하지 않는 것을 제외하고는, 상기 제조예 1 내지 3과 동일한 방법으로 나노섬유 멤브레인을 제조하였다.       A nanofiber membrane was prepared in the same manner as in Preparation Examples 1 to 3 except that the heat treatment was not performed.

실시예Example 2: 본 발명  2: invention 폴리테트라플루오르에틸렌Polytetrafluoroethylene 나노섬유  Nanofiber 멤브레인의Membrane 특성 분석 Character analysis

본 실시예 2의 실험 결과는 (a) 비교예 1의 PEO/PTFE 혼합 나노섬유 멤브레인, (b) 제조예 1의 PEO/PTFE 혼합 나노섬유를 200℃에서 열처리한 멤브레인, (c) 제조예 2의 PEO/PTFE 혼합 나노섬유를 300℃에서 열처리한 멤브레인, (d) 제조예 3의 PEO/PTFE 혼합 나노섬유를 330℃에서 열처리한 멤브레인의 순서로 나타냈다.The experimental results of Example 2 show that (a) PEO / PTFE mixed nanofiber membrane of Comparative Example 1, (b) membrane heat-treated at 200 ° C of the PEO / PTFE mixed nanofibers of Preparation Example 1, (c) (D) PEO / PTFE mixed nanofibers of Preparation Example 3 were heat-treated at 330 ° C in that order.

실험예Experimental Example 1: 본 발명  1: invention 폴리테트라플루오르에틸렌Polytetrafluoroethylene 나노섬유  Nanofiber 멤브레인의Membrane 표면 분석 Surface analysis

본 발명 비분해성 나노섬유 멤브레인들의 형태를 분석은 상기 제조예 1 내지 제조예 3 및 비교예 1에 따라 제조된 본 발명 비분해성 나노섬유 멤브레인 각 표면을 주사전자현미경(SEM, JSM-6335F, JEOL, 15.0kV, ×3,000), 에너지 분산형 X선 분광법(EDX, S-4300, Hitachi, 15.0kV) 및 전반사 측정 푸리에 변환 적외선 분광법(ATR-FTIR, ALPHA, Bruker Optics, 400-4000nm)을 이용하여 관찰하는 방법을 통하여 수행하였다.The analysis of the non-degradable nanofiber membranes of the present invention was carried out by scanning electron microscopy (SEM, JSM-6335F, JEOL, JEOL, etc.) on the surfaces of the non-degradable nanofiber membranes prepared according to Preparation Examples 1 to 3 and Comparative Example 1, (ATR-FTIR, ALPHA, Bruker Optics, 400-4000 nm) and total reflection measurement were performed using an energy dispersive X-ray spectroscopy (EDX, S-4300, Hitachi and 15.0 kV) .

실험결과, 도 1(a) PEO/PTFE 혼합 나노섬유 멤브레인의 경우 500 nm정도의 균일한 섬유 굵기의 분포를 보여주며 무질서한 방향으로 섬유가 배열된 부직포 형태에 섬유의 표면에는 PTFE의 첨가에 의한 입자 형태가 관찰되며, (b) 200℃에서 열처리한 나노섬유 멤브레인과 (c) 300℃에서 열처리한 나노섬유 멤브레인의 경우 1μm 전후의 섬유 굵기의 분포를 보여주며 열처리 후에도 섬유 형태를 유지하는 것을 확인할 수 있으며, 열처리 이전보다 섬유 표면의 거칠기가 증가한 것이 관찰되었다. (d) 330℃에서 열처리한 나노섬유 멤브레인의 경우 500 nm∼1μm의 섬유 굵기 분포를 보여주며 고온에서 열처리를 했지만 나노섬유 형태를 유지하고 있었다.The results show that the PEO / PTFE mixed nanofiber membrane exhibits a uniform fiber thickness distribution of about 500 nm. In the non-woven fabric in which the fibers are arranged in disordered directions, (B) Nanofiber membranes annealed at 200 ° C and (c) nanofiber membranes annealed at 300 ° C show a distribution of fiber thicknesses of around 1 μm and retain fiber morphology after heat treatment , And it was observed that the roughness of the fiber surface was increased before the heat treatment. (d) Nanofiber membranes annealed at 330 ℃ show a fiber thickness distribution of 500 nm ~ 1μm and maintained heat-treated at high temperature, but in nanofiber form.

상기 제조예 1 내지 제조예 3 및 비교예 1에 따라 제조된 본 발명 비분해성 나노섬유 멤브레인의 원소정보는 EDX를 이용하여 분석하였다.  The elemental information of the non-degradable nanofiber membranes prepared according to Preparation Examples 1 to 3 and Comparative Example 1 was analyzed using EDX.

실험결과, 도 2(a) PEO/PTFE 혼합 나노섬유 멤브레인의 경우 PEO에 의한 0.26keV에서 C피크와 0.52keV에서 O피크를 확인할 수 있었으며, PTFE에 의한 0.26keV에서 C피크와 0.68keV에서 F피크를 확인할 수 있었다. (b) 내지 (d)에서는 PTFE에 의한 0.26keV에서 C피크와 0.68keV에서 F피크만을 관찰할 수 있었다. 이를 통하여 열처리에 의해 PEO가 제거되었음을 확인하였다.As a result, it was confirmed that the PEO / PTFE mixed nanofiber membrane showed O peak at 0.26 keV at C peak and 0.52 keV at 0.26 keV, and peak C at 0.26 keV by PTFE and F peak at 0.68 keV . (b) to (d), only C peak at 0.26 keV by PTFE and F peak at 0.68 keV were observed. Through this, it was confirmed that PEO was removed by heat treatment.

상기 제조예 1 내지 제조예 3 및 비교예 1에 따라 제조된 본 발명 비분해성 나노섬유 멤브레인의 흡광도는 ATR-FTIR을 이용하여 측정하였다The absorbance of the non-degradable nanofiber membrane prepared according to Preparation Examples 1 to 3 and Comparative Example 1 was measured using ATR-FTIR

실험결과, 도 3(a) PEO/PTFE 혼합 나노섬유 멤브레인의 경우 843, 1280 및 947cm-1에서 PEO 특이 피크를 관찰할 수 있으며, 1466cm-1에서 C-H bending vibration 피크, 1349, 1280 및 1249cm-1에서 O-H bending vibration 피크와 C-H stretching vibration 피크를 관찰됨으로써 PEO 특성화가 확인되었다. -CF2- stretching vibrations 피크가 1203 및 1146cm-1에서 관찰되어 PTFE특성화가 확인되었다. (b) 내지 (d)에서는 PEO의 피크가 제거된 것을 관찰할 수 있으며, 이는 열처리에 의한 제거임을 확인할 수 있었다.Experimental results Figure 3 (a) PEO / PTFE blends of the nanofiber membrane 843, it is possible to observe the PEO specific peaks at 1280 and 947cm -1, CH bending vibration peak, 1349, 1280 and 1249cm -1 1466cm -1 in And the PE bending vibration peak and the CH stretching vibration peak were observed. The -CF 2 - stretching vibrations peaks were observed at 1203 and 1146 cm -1 , confirming PTFE characterization. In (b) to (d), it can be seen that the peaks of PEO were removed and it was confirmed that the peaks were removed by heat treatment.

실험예Experimental Example 2: 본 발명  2: invention 폴리테트라플루오르에틸렌Polytetrafluoroethylene 나노섬유  Nanofiber 멤브레인의Membrane 열중량Thermal weight 분석 analysis

본 발명에 따른 비분해성 나노섬유 멤브레인들의 형태 분석은 상기 제조예 1 내지 제조예 3 및 비교예 1에 따라 제조된 본 발명 비분해성 나노섬유 멤브레인을 열중량분석기(TGA, TG-1280, Rigaku, 800℃)을 이용하여 관찰하는 방법을 통하여 수행하였다. The non-degradable nanofiber membranes according to the present invention were analyzed using a thermogravimetric analyzer (TGA, TG-1280, Rigaku, 800) according to the Preparation Examples 1 to 3 and Comparative Example 1, ℃) was used for the observation.

실험결과, 도 4(a) PEO/PTFE 혼합 나노섬유 멤브레인의 경우 150℃에서 PEO의 제거에 의한 급격한 중량 감소를 나타내며, 500℃에서 PTFE의 제거에 의한 중량 감소를 관찰할 수 있었다. (b) 내지 (d)에서는 200, 300 및 330℃ 각각의 열처리에 의해서 PEO가 제거되어 500℃에서 PTFE의 제거에 의한 중량 감소만을 관찰할 수 있었다.Experimental results show that the PEO / PTFE mixed nanofiber membrane exhibits a rapid weight loss due to the removal of PEO at 150 ° C and a weight loss due to PTFE removal at 500 ° C is observed in FIG. 4 (a). (b) to (d), PEO was removed by heat treatment at 200, 300, and 330 ° C., respectively, and only the weight reduction due to PTFE removal at 500 ° C. was observed.

실험예Experimental Example 3: 본 발명  3: invention 폴리테트라플루오르에틸렌Polytetrafluoroethylene 나노섬유  Nanofiber 멤브레인의Membrane 결정구조 분석 Crystal structure analysis

본 발명에 따른 비분해성 나노섬유 멤브레인들의 형태 분석은 상기 제조예 1 내지 제조예 3 및 비교예 1에 따라 제조된 본 발명 비분해성 나노섬유 멤브레인을 X선 회절장치(XRD, D/MAX-2500/PC, Rigaku, 60kV, 300mA)을 이용하여 관찰하는 방법을 통하여 수행하였다. The non-degradable nanofiber membranes according to the present invention were analyzed by X-ray diffraction (XRD, D / MAX-2500 / PC, Rigaku, 60 kV, 300 mA).

실험결과, 도 5(a) PEO/PTFE 혼합 나노섬유 멤브레인의 경우 17, 18° 근처에서 PEO 결정 피크가 관찰되었으며, (b) 200℃에서 열처리한 나노섬유 멤브레인에서도 PEO 결정 피크가 관찰되었다. (c), (d)에서는 PEO 결정 피크가 사라지고 17.5, 18.5°근처에서 PTFE 결정 구조가 관찰되었다. 이를 통해서 300℃ 이전의 열처리에 의해서 PEO는 제거되지만 PEO의 결정 구조를 나타내는 것과 300℃ 이후의 열처리에 의해서 PTFE의 결정 구조가 나타나는 것을 확인하였다.
The PEO / PTFE mixed nanofiber membrane showed PEO crystal peaks at 17 and 18 °, and (b) PEO crystal peaks at 200 ° C. (c) and (d), the PEO crystal peaks disappeared, and the PTFE crystal structure was observed near 17.5 and 18.5 °. Through this, it is confirmed that the crystal structure of PTFE is shown by the heat treatment before 300 ° C, but the PEO crystal structure and the heat treatment after 300 ° C show the crystal structure of PTFE.

실험예Experimental Example 4: 본 발명  4: invention 폴리테트라플루오르에틸렌Polytetrafluoroethylene 나노섬유  Nanofiber 멤브레인의Membrane 생체적합성 조사 Biocompatibility survey

상기 제조예 1 내지 제조예 3 및 조직 배양 플레이트(TCP)에 따라 제조된 본 발명 비분해성 나노섬유 멤브레인의 생체적합성은 조골세포(MC3T3-E1, ATCC)를 사용하여 평가하였다.Biocompatibility of the non-degradable nanofiber membrane of the present invention prepared according to Preparation Examples 1 to 3 and the tissue culture plate (TCP) was evaluated using osteoblasts (MC3T3-E1, ATCC).

4.1 세포의 증식력과 부착력 측정 4.1 Measurement of cell proliferation and adhesion

조골세포는 10% 우태아 혈청(FBS)과 1% 페니실린-스트렙토마이신이 첨가된 α-MEM에서 배양되었다.Osteoblast cells were cultured in α-MEM supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin.

상기 제조예 1 내지 제조예 3 및 TCP에 따라 제조된 본 발명 비분해성 나노섬유 멤브레인은 UV를 이용하여 멸균처리한 다음 무균상태에서 75%, 50%, 25% 에탄올로 각각 소독하고 인산완충식염수(PBS)를 이용하여 2회 세척하여 준비하였다. The non-degradable nanofiber membrane of the present invention prepared according to Preparation Examples 1 to 3 and TCP was sterilized using UV, sterilized with 75%, 50%, and 25% ethanol in an aseptic state, and washed with phosphate buffered saline PBS) for two times.

상기 방법에 따라 멸균된 본 발명 비분해성 나노섬유 멤브레인을 24-well 플레이트 바닥에 밀착시킨 다음, 본 발명 비분해성 나노섬유 멤브레인의 표면에서만 세포접착이 일어날 수 있도록, 유리링을 비분해성 나노섬유 멤브레인 위에 밀착시켰다. 상기와 같이 준비된 세포배양용 24 -well 플레이트에 조골세포를 5 X 104 cells/well의 농도로 본 발명 비분해성 나노섬유 멤브레인에 올려진 유리링 안쪽으로 분주하고 37 ℃, 5 % CO2 환경에서 4시간, 1, 3, 5, 7일 동안 각각 배양하여 세포의 부착 및 증식 능력을 MTT법을 이용하여 평가하였다.The sterilized non-degradable nanofiber membrane of the present invention was brought into close contact with the bottom of a 24-well plate, and then the glass ring was immersed in the non-degradable nanofiber membrane Respectively. Prepared as described above, the osteoblast cells in 24 -well plates incubated 5 X 10 4 cells / well to a concentration of the present invention non-degradable nanofibers dispensed into a glass ring mounted on the inside of the membrane, and 37 ℃, 5% CO 2 environment 4 hours, 1, 3, 5, and 7 days, respectively. Cell adhesion and proliferation were evaluated by MTT assay.

실험결과, 조골세포의 초기 4시간 내지 1일, 3일 부착은 도 6(b) 200℃에서 열처리한 나노섬유 멤브레인과 (c) 300℃에서 열처리한 나노섬유 멤브레인에서 큰 차이 없이 비슷한 경향을 나타내며, TCP와 (d) 330℃에서 열처리한 나노섬유 멤브레인에서 높게 나타나는 경향을 확인할 수 있었다. TCP와 (d) 330℃에서 열처리한 나노섬유 멤브레인에서 높게 나타나는 경향은 실험에서 전체적으로 나타나는 것을 확인하였고, 5일 및 7일에서 격차가 크게 나타나는 것도 확인할 수 있었다.As a result, the initial 4 hours to 1 day and 3 days attachment of the osteoblast showed similar tendency in the nanofiber membrane annealed at 200 ° C and the nanofiber membrane annealed at 300 ° C in FIG. 6 (b) , TCP and (d) nanofiber membranes annealed at 330 ℃. TCP and (d) Nanofiber membranes heat treated at 330 ℃ showed a high tendency in the experiment as a whole, and it was confirmed that the gap was large at 5 days and 7 days.

생체적합성 평가결과는 조골세포의 초기 점착은 도 7(b) 200℃에서 열처리한 나노섬유 멤브레인과 (c) 300℃에서 열처리한 나노섬유 멤브레인보다 (d) 330℃에서 열처리한 나노섬유 멤브레인이 조금 많은 세포의 부착률을 나타냈다. 그리고 5일이 경과한 이후부터는 (d) 330℃에서 열처리한 나노섬유 멤브레인의 세포 부착률이 현저하게 높아지는 것을 확인할 수 있었다.The results of the biocompatibility test show that the initial adhesion of osteoblasts is less than that of nanofiber membranes annealed at 200 ° C and (c) nanofiber membranes annealed at 300 ° C. (D) Nanofiber membranes annealed at 330 ° C Many cell adhesion rates were observed. After 5 days, it was confirmed that (d) the cell adhesion rate of the nanofiber membrane subjected to heat treatment at 330 ° C was remarkably increased.

본 발명 PTFE 비분해성 나노섬유 멤브레인 열처리 온도별로 나타낸 결과는 330℃에서 열처리된 본 발명 PEO/PTFE 혼합 나노섬유를 330℃에서 열처리한 멤브레인(d)의 생체적합성이 가장 우수하게 나타났다.
The results of the PTFE non-degradable nanofiber membrane according to the present invention show the best biocompatibility of the membrane (d) annealed at 330 ° C according to the present invention PEO / PTFE mixed nanofiber heat-treated at 330 ° C.

4.2 세포의 분화력 측정 4.2 Measurement of cell division power

본 발명 PTFE 비분해성 나노섬유 멤브레인의 조골세포의 분화능 평가는 알칼린 포스파타제(ALP) 활성 실험을 이용하여 검정하였다.The evaluation of the osteoblast differentiation potential of the PTFE non-degradable nanofiber membrane of the present invention was carried out using an alkaline phosphatase (ALP) activity test.

상기 실험예 4.1 세포의 증식력과 부착력 측정과 동일한 방법으로 준비된 세포배 양용 24-well 플레이트에 조골세포를 5 X 104 cells/well 의 농도로 분주하고, 배지로는 10% 우태아 혈청(FBS)과 1% 페니실린-스트렙토마이신이 첨가된 α-MEM을 사용하여 3, 5, 7, 14일 동안 각각 배양하였다. 상기 각각의 기간 동안 세포를 배양한 다음에 배지를 제거하고 나노섬유 멤브레인 표면에 남아있는 세포를 계면활성제를 이용하여 용해시키고 용해물의 상층액을 취하여 ALP Assay KIT (DALP-250, GENTAUR)를 이용하여 흡광도를 측정함으로써 ALP 활성 정도를 측정하였다. 단, 필요한 부분에서는 부분적으로 본 실험에 적합하도록 재설계하였다. 재현성 검토를 위해서 각 비분해성 나노섬유 멤브레인마다 동일한 시료를 사용하여 상기 모든 테스트를 수행하였다.Experimental Example 4.1 Osteoblast cells were seeded at a concentration of 5 × 10 4 cells / well on a 24-well plate for cell culture prepared by the same method as that of measuring cell proliferation and adhesion, and 10% fetal bovine serum (FBS) And 1% penicillin-streptomycin-supplemented α-MEM for 3, 5, 7, and 14 days, respectively. Cells were cultured for each period, then the medium was removed, and the cells remaining on the surface of the nanofiber membrane were dissolved using a surfactant, and the supernatant of the lysate was taken using ALP Assay KIT (DALP-250, GENTAUR) And the degree of ALP activity was measured by measuring the absorbance. However, it was partially redesigned to be suitable for this experiment. All of the above tests were performed using the same sample for each non-degradable nanofiber membrane for reproducibility review.

실험결과, 도 8(b) 200℃에서 열처리한 나노섬유 멤브레인과 (c) 300℃에서 열처리한 나노섬유 멤브레인의 경우 3일 내지 7일에서 큰 차이를 보이지 않았으며, (d) 330℃에서 열처리한 나노섬유 멤브레인의 ALP 농도가 가장 높은 것을 확인할 수 있었다. 초기 7일까지는 (d) 330℃에서 열처리한 나노섬유 멤브레인에서 조골세포의 분화력이 가장 높은 것을 확인할 수 있는 부분이었다. 14일에는 TCP의 ALP 농도가 가장 높게 나타났으며, 열처리한 나노섬유 멤브레인을 사용한 경우 (d) 330℃에서 열처리한 나노섬유 멤브레인의 ALP 농도가 가장 높게 나오는 것으로 보아, 조골세포의 분화에 가장 적합한 것을 확인할 수 있었다. As a result, in the case of the nanofiber membrane annealed at 200 ° C and the nanofiber membrane annealed at 300 ° C, no significant difference was observed between 3 days and 7 days. (D) It was confirmed that the ALP concentration of one nanofiber membrane was the highest. (D) It was confirmed that the osteoblast differentiation ability was the highest in the nanofiber membrane annealed at 330 ° C until the early 7th day. On the 14th day, the highest concentration of ALP in TCP was observed. In the case of using heat-treated nanofiber membrane, (d) ALP concentration of nanofibrous membrane annealed at 330 ℃ was the highest, .

4.3 세포의 골형성력 측정 4.3 Measurement of bone formation capacity of cells

본 발명 PTFE 비분해성 나노섬유 멤브레인의 조골세포의 골형성력 평가는 알리자린 레드 에스(ARS) 부착 실험을 이용하여 검정하였다.Evaluation of bone forming ability of osteoblast of the PTFE non-degradable nanofiber membrane of the present invention was performed using an alizarin red s (ARS) adhesion experiment.

상기 실험예 세포의 증식력과 부착력 측정과 동일한 방법으로 준비된 세포배 양용 24-well 플레이트에 조골세포를 5 X 104 cells/well 의 농도로 분주하고, 배지로는 10% 우태아 혈청(FBS)과 1% 페니실린-스트렙토마이신이 첨가된 α-MEM을 사용하여 3, 5, 7, 14일 동안 각각 배양하였다. 상기 각각의 기간 동안 세포를 배양한 다음에 배지를 제거하고 나노섬유 멤브레인 표면에 남아있는 세포를 4% 포름알데하이드를 이용하여 고정시키고, 알리자린 레드 에스(ARS, Sigma-Aldrich Co.)를 pH 4.1, 40 mM 용액으로 만들어 처리하였다. 처리 후 세틸피리디늄클로라이드 (CPC, Sigma-Aldrich Co.)를 10wt.% 용액으로 만들어 처리하여 정량화하였다.The osteoblast cells were plated at a concentration of 5 × 10 4 cells / well on a 24-well plate for cell culture prepared in the same manner as the cell growth and adhesion, and the cells were cultured in a 10% fetal bovine serum (FBS) And cultured for 3, 5, 7, and 14 days with α-MEM supplemented with 1% penicillin-streptomycin. Cells were cultured for each of the above periods, and the medium was removed. The cells remaining on the surface of the nanofiber membrane were fixed with 4% formaldehyde, and alizarin reds (ARS, Sigma-Aldrich Co.) 40 mM solution. After treatment, cetylpyridinium chloride (CPC, Sigma-Aldrich Co.) was treated with 10 wt% solution and quantified.

실험결과, 골형성의 경향은 초기 3일과 5일 사이에서 빠르게 나타난 후에 느려지는 것을 확인할 수 있었으며, 5일과 7일은 유사한 수준을 보여주는 것을 확인할 수 있었다(도 9). 골형성에 있어서 (b) 200℃에서 열처리한 나노섬유 멤브레인과 (c) 300℃에서 열처리한 나노섬유 멤브레인의 경향은 이전의 실험과는 다르게 (c) 300℃에서 열처리한 나노섬유 멤브레인에서 높게 나타나는 것을 확인할 수 있었다. 그리고 TCP의 골형성력이 가장 낮게 나타났다. 결과적으로 조골세포에 의한 골형성은 이전의 실험과 유사하게 (d) 330℃에서 열처리한 나노섬유 멤브레인에서 가장 높게 나타났다. As a result of the experiment, it was confirmed that the tendency of bone formation slowed down rapidly between early 3 days and 5 days, and that 5 days and 7 days showed a similar level (FIG. 9). (B) the tendency of the nanofiber membrane annealed at 200 ° C and (c) the nanofiber membrane annealed at 300 ° C in the bone formation, (c) the tendency of the nanofiber membrane annealed at 300 ° C . And the bone formation capacity of TCP was the lowest. As a result, bone formation by osteoblasts was the highest in the nanofiber membranes annealed at 330 ° C, similar to previous experiments (d).

4.4 염증반응성 평가 4.4 Evaluation of inflammatory reactivity

상기 제조예 1 내지 제조예 3 및 TCP에 따라 제조된 본 발명 비분해성 나노섬유 멤브레인의 염증반응성은 리포폴리사카라이드(LPS)로 염증반응이 유도된 mouse유래 탐식세포인 RAW264.7 세포를 이용하여 검정하였다.The inflammatory reactivity of the non-degradable nanofiber membrane of the present invention prepared according to Preparation Examples 1 to 3 and TCP was determined by using RAW264.7 cells, which are mouse-derived macrophages induced by inflammatory reaction with lipopolysaccharide (LPS) Respectively.

Murine macrophage cell line인 RAW264.7 세포를 페니실린(100 IU/㎖) 및 스트렙토마이신(100 ㎍/㎖)과 10%의 FBS를 함유한 DMEM 배지를 이용해서 5 X 104 cells/well 조절한 후, 상기 제조예 1 내지 제조예 3 및 TCP에 따라 제조된 본 발명 비분해성 나노섬유 멤브레인이 들어가 있는 24-well 플레이트에 접종하고, 5% CO2 및 37℃에서 48시간 동안 전 배양하였다.Murine macrophage cell line RAW264.7 cells were cultured at 5 × 10 4 cells / well in DMEM medium containing penicillin (100 IU / ml) and streptomycin (100 μg / ml) and 10% FBS, The plate was inoculated on a 24-well plate containing the non-degradable nanofiber membrane of the present invention prepared according to Preparation Examples 1 to 3 and TCP, and pre-cultured at 5% CO 2 and 37 ° C for 48 hours.

IL-6의 정량은 LPS로 염증반응이 유도된 Raw 264.7 세포(1 X 105 cells/well)의 배양액을 이용하여 실시하였다. 상기 배양 배지 50 ㎕를 IL-6 단백질 항체가 부착된 플레이트에 분주 한 다음 ELISA kit(R&D Systems)를 통하여 측정하였다.Quantification of IL-6 was performed using Raw 264.7 cells (1 × 10 5 cells / well) in which inflammation was induced by LPS. 50 [mu] l of the above culture medium was dispensed on a plate having an IL-6 protein antibody, and then measured using an ELISA kit (R & D Systems).

실험결과, 플레이트에 탐식세포만을 배양한 TCP에서 IL-6의 방출이 가장 낮게 나타났다(도 10). (c) 300℃에서 열처리한 나노섬유 멤브레인과 (d) 330℃에서 열처리한 나노섬유 멤브레인에서 배양된 탐식세포의 IL-6의 방출은 TCP와 유사한 수준인 것을 확인할 수 있었다. (b) 200℃에서 열처리한 나노섬유 멤브레인에서 IL-6의 방출이 가장 높게 나타났는데, 염증활성이 가장 높게 나타내는 것을 확인할 수 있는 결과이다. (c)와 (d)는 TCP와 유사한 정도의 낮은 염증활성을 나타내는 것을 확인할 수 있었다.
As a result, the release of IL-6 was the lowest in the TCP cultured with only phagocytic cells on the plate (FIG. 10). (c) Nanofiber membranes annealed at 300 ° C and (d) nanofiber membranes annealed at 330 ° C showed that IL-6 release was similar to that of TCP. (b) The highest release of IL-6 was observed in nanofiber membranes heat treated at 200 ° C, indicating that inflammatory activity is the highest. (c) and (d) showed low inflammation activity similar to that of TCP.

본 발명은 폴리테트라플루오르에틸렌을 포함하는 골유도재생술용 비분해성 나노섬유 멤브레인 및 이의 제조방법에 관한 것으로서, 생체적합성, 기계적 강도, 유연성, 다공성 및 낮은 염증반응성을 갖는 비분해성 나노섬유 멤브레인을 제공함으로 생물의약소재 산업상 매우 유용한 발명이다.Disclosed is a non-degradable nanofiber membrane for bone induction regeneration comprising polytetrafluoroethylene, and a method for preparing the same. The non-degradable nanofiber membrane has biocompatibility, mechanical strength, flexibility, porosity and low inflammation reactivity. It is a very useful invention in the biopharmaceutical material industry.

Claims (6)

증류수에 폴리에틸렌옥사이드(Polyethyleneoxide; PEO)를 용해시켜 폴리에틸렌옥사이드 수용액을 형성하는 단계와; 상기 단계에서 얻은 폴리에틸렌옥사이드 수용액에 폴리테트라플루오르에틸렌 Polytetrafluoroethylene(PTFE) 수분산액을 물에 혼합하여 PEO/PTFE 혼합 용액을 제조하는 단계와; 상기 단계에서 얻은 PEO/PTFE 혼합 용액의 고형분을 용매인 물에 대하여 20wt.%로 고정하고 24시간 교반하여 PEO/PTFE 고분자 혼합 교반용액을 제조하는 단계와; 상기 단계에서 얻은 고분자 혼합 교반용액을 전기방사하여 비분해성 나노섬유를 수득하는 단계와; 상기 단계에서 얻은 비분해성 나노섬유를 300℃ 이상에서 승온조건으로 열처리하여 폴리테트라플루오르에틸렌(PTFE)만을 남기면서 나노섬유 형태를 유지하는 단계로 이루어지는 나노섬유 멤브레인 제조방법에 있어서;
상기 PEO/PTFE 고분자 혼합 교반용액 제조단계에서 PEO와 PTFE의 혼합비를 1:2 ~ 1:5(w/w)로 하고 비분해성 나노섬유 유지단계에서 열처리는 실온에서 200℃까지는 100℃/h의 승온조건으로 열처리하고 200℃에 도달하면 10분간 유지하고 300℃까지는 20℃/h의 승온조건으로 열처리하고 300℃에 도달하면 10분간 유지하고 다시 300℃에서 20℃/h 승온조건으로 330℃까지 처리하여 330℃ 도달하면 10분간 330℃를 유지하는 것이 특징인 골유도재생술용 나노섬유 멤브레인 제조방법.
Dissolving polyethylene oxide (PEO) in distilled water to form an aqueous solution of polyethylene oxide; Mixing a polytetrafluoroethylene polytetrafluoroethylene (PTFE) aqueous dispersion solution with water in the polyethylene oxide aqueous solution obtained in the above step to prepare a PEO / PTFE mixed solution; The solid content of the PEO / PTFE mixed solution obtained in the above step is fixed at 20 wt.% With respect to water as a solvent and stirred for 24 hours to prepare a PEO / PTFE polymer mixed solution. Dissolving the polymer mixed solution obtained in the above step in an electrospun to obtain non-degradable nanofibers; Treating the non-degradable nanofibers obtained in the above step at a temperature of 300 ° C or higher to maintain the nanofiber shape while leaving only polytetrafluoroethylene (PTFE);
The mixing ratio of PEO to PTFE is 1: 2 to 1: 5 (w / w) in the PEO / PTFE polymer mixed solution preparation step, and the heat treatment in the non-degradable nanofiber holding step is performed at 100 ° C / h When the temperature reached 200 캜, it was maintained for 10 minutes. When the temperature reached 300 캜, the furnace was maintained at a temperature of 20 캜 / h for up to 300 캜. And maintaining the temperature at 330 ° C for 10 minutes when the temperature reaches 330 ° C.
삭제delete 삭제delete 삭제delete 제 1항의 방법에 따라 제조된 생체적합성이 증대된 것이 특징인 골유도 재생용 나노섬유 멤브레인.A nanofiber membrane for bone induction and regeneration, characterized in that the biocompatibility is increased according to the method of claim 1. 삭제delete
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