초록

본 연구는 심혈관 질환을 치료하기 위한 약물용출 스텐트에 관한 것이다. 약물이 코팅된 스텐트를 전임상 동물실험을 통해 검증하는 과정에서 다양한 분석기법을 활용하는 내용이다. 우선 시험관내 시험을 통해 세포(A10, HUVEC)에 미치는 약물의 효과를 확인하였을 때 정상적인 증식양상이 확인되였다. 토끼 실험을 통한 약물 용출 스텐트의 효능을 확인하였고 이 과정에서 미세단층촬영기를 이용한 새로운 분석기법을 고안하여 시행하였다. 그 결과 약물 용출 스텐트 그룹에서 금속스텐트에 비해 재협착율이 줄어든 것이 확인되었다.

Abstract ▼

The aim of this study was to evaluate the effect of drug-eluting stent using various analysis tool in animal study.
First of all, we investigate the cytotoxicity of drugs on A10 or HUVEC cell proliferation. As results, it was not showed any abnormal cell morphology and cell proliferation profile

The aim of this study was to evaluate the effect of drug-eluting stent using various analysis tool in animal study.
First of all, we investigate the cytotoxicity of drugs on A10 or HUVEC cell proliferation. As results, it was not showed any abnormal cell morphology and cell proliferation profile compare to that of general cell proliferation. Moreover, when we investigate the platelet adhesion to stent material coated drug or bare metal, it was observed noticeable reducing of platelet adhesion on drug coated material compare to that of bare metal.
Based on in vitro investigation as above, pre-clinical animal study was carried out. The animal employed was New Zealand White Rabbit. The route for stent implantation was carotid artery, aorta and iliac artery. Drug-eluting stent and bare metal stent was implanted to left and right iliac artery randomly. Entire process of animal study was performed under optimized condition with angiography machine, EKG and so on. Four weeks post-implantation, rabbits were sacrifed, and tissue surround stents were harvested. For pathological analysis, H&E staining and Carstair's staining were performed. As results, it was hard to detect the statistical difference between drug eluting stent and bare meta stent with various parameter. Since the experimental number was few (n=3), additional experiment is on-going.
To investigate the strut covering rate of stents, lumen of stents was subjected to scanning electron microscope. To reduce the error of scanning electron microscope focuing by phase difference, the one side part of stents were cut longitudinally and spread to 2-dimension. As results, much of exposing of stent strut was observed at drug-eluting stent group compare to that of bare metal stent. It caused by the inhibition of cell proliferation by drug, and cell migration to lumen of stent was arrest.
For the more acute analysis for restenosis, micro-computed tomography was used. To arouse the difference Hounsfield Unit (HU) between subjects such as tissue, stent material, contrast medium was injected to lumen of stents. Thereafter, restenosis was defined by calculating three parts mentioned above was subtracted from total volume under 2-dimensional image. As results, the length of expanded stent was 4 mm in width and 17 mm in height. It is correspond to injury score of pathological analysis. Moreover, less restenosis was observed at drug-eluting stent compare to that of bare metal stent with the unaided eye. And when the investigate the position-by-position quantitative analysis, higher restenosis was showed at the proximal area of bare metal stent. While it was observed that the restenosis was evenly distributed at whole area of drug-eluting stent. It is caused by dispersing the drug to overall of stent surface with electro-sprayer, and the effect of drug has inhibitory effect on cell proliferation.

목차 Contents

• 표지 ... 1
• 제출문 ... 3
• 보고서 요약서 ... 4
• 요약문 ... 5
• SUMMARY ... 6
• 6. 연구 성과 실적 및 향후 계획 ... 7
• 6.1 총괄연구개발과제의 연구성과 실적 및 향후 계획 ... 7
• 6.2 연구성과 유형별 세부 내역 ... 8
• 7. 참여연구원 현황표 ... 11
• [별지 제3호 서식] 보건의료기술진흥사업 최종보고서 서식 ... 12
• II. 총괄연구과제 연구결과 ... 13
• 1. 연구개발과제의 배경 및 필요성 ... 14
• 2. 국내외 기술개발 현황 ... 16
• 3. 연구개발과제의 추진체계 ... 17
• 4. 연구개발수행 내용 및 결과 ... 18
• 5. 목표달성도 및 관련분야 기여도 ... 25
• 6. 향후 연구성과 추진 계획 ... 27
• 7. 연구개발결과의 파급효과 ... 27
• 8. 연구개발결과의 활용계획 ... 29
• 9. 연구개발과정에서 수집한 해외과학기술정보 ... 29
• 10. 참고문헌 ... 30
• IV. 첨부서류 ... 32
• 끝페이지 ... 37