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Sequential dual-drug delivery of BMP-2 and alendronate from hydroxyapatite-collagen scaffolds for enhanced bone regeneration : 효과적인 골재생을 위한 hydroxyapatite-collagen 스케폴드를 이용한 BMP-2 와 alendronate 의 순차적 이중 약물 전달

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dc.contributor.advisor장학-
dc.contributor.authorMAIERDANJIANG WUFUER-
dc.date.accessioned2021-11-30T04:55:07Z-
dc.date.available2021-11-30T04:55:07Z-
dc.date.issued2021-02-
dc.identifier.other000000165523-
dc.identifier.urihttps://hdl.handle.net/10371/176099-
dc.identifier.urihttps://dcollection.snu.ac.kr/common/orgView/000000165523ko_KR
dc.description학위논문 (박사) -- 서울대학교 대학원 : 의과대학 의학과, 2021. 2. 장학.-
dc.description.abstractThe clinical use of bioactive molecules in bone regeneration has been known to have side effects, which result from uncontrolled and supraphysiological doses. In this study, we demonstrated the synergistic effect of two bioactive molecules, bone morphogenic protein-2 (BMP-2) and alendronate (ALN), by releasing them in a sequential manner. Collagen-hydroxyapatite composite scaffolds functionalized using BMP-2 are loaded with biodegradable microspheres where ALN is encapsulated. The results indicate an initial release of BMP-2 for a few days, followed by the sequential release of ALN after two weeks. The composite scaffolds significantly increase osteogenic activity owing to the synergistic effect of BMP-2 and ALN. Enhanced bone regeneration was identified at eight weeks post-implantation in the rat 8-mm critical-sized defect. Our findings suggest that the sequential delivery of BMP-2 and ALN from the scaffolds results in a synergistic effect on bone regeneration, which is unprecedented. Therefore, such a system exhibits potential for the application of cell-free tissue engineering.-
dc.description.abstract골형성을 위해 사용하는 생리활성 분자는 생리학적으로 사용되는 용량을 초과하여 사용할 경우 임상적인 부작용이 있는 것으로 알려졌다. 본 연구에서는 생체 활성 분자인 BMP-2 (Bone morphogenic protein-2) 와 alendronate (ALN)를 순차적으로 방출하여 in vitro 및 in vivo에서의 시너지 효과를 보여줍니다.
개발된 약물전달체는 BMP-2를 탑재한 Collagen-hydroxyapatite scaffold에 ALN 탑재된 생분해성 마이크로 스피어를 삽이하여 제작되었습니다. 개발된 약물전달체의 약동학적 특성을 분석해보니, BMP-2는 0~7일 사이 방출이 완료되었고 ALN은 14~21일 사이 방출이 완료되어 순차방출이 되는 것을 확인 할 수 있었습니다. 또한 단일 약물의 사용보다 BMP-2와 ALN의 순차방출시 골 재생 효과가 뛰어났음을 8 mm의 임계 골결손 rat 모델을 8주간 관찰한 결과 확인 할 수 있었습니다. 본 연구는 BMP-2 와 ALN의 순차적 전달이 효과적인 골 재생에 뛰어난 효과를 가져옴을 시사합니다.
이러한 시간차 약물방출 시스템은 세포를 사용하지 않는 조직 공학 재료로써의 응용 가능성을 보여줍니다.
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dc.description.tableofcontentsABSTRACT ⅰ
CONTENTS ⅲ
LIST OF FIGURES AND TABLES. ⅳ
INTRODUCTION. 1
MATERIALS AND METHODS
Materials 5
CHAS fabrication. 5
Drug release kinetics of BMP-2 in CHAS. 6
Drug release kinetics of ALN in CHAS 7
Preparation of PLGA microspheres 8
Cell cultures & Cell viability test 8
Alkaline phosphatase (ALP) activity assay. 9
Animal model and surgical procedures. 9
Micro-computed tomography (μ-CT) Analysis 11
Sample preparation and histological analysis 12
Statistical analysis. 12
RESULTS
Development of a sequential dual delivery system for BMP-2 and ALN in CHAS. 13
In vitro release of BMP-2 and ALN from CHAS 14
In vitro osteogenesis study. 14
μ-CT analysis 16
Histological analysis. 17
DISCUSSION 18
CONCLUSION 21
REFERENCE. 23
ABSTRACT IN KOREAN. 42
LIST OF FIGURES
Figur1. Schematic illustration of sequential dual-drug delivery using BMP-2 and ALN. 29
Figur2. Morphological analysis of CHAS. 31
Figur3. Drug release test. 32
Figur4. Cell viability evaluation. 33
Figur5. μ-CT radiographic evaluation.34
Figur6. Quantitative analysis of new bone volume 35
Figur7. Histological evaluation of bone regeneration in rat calvarial defects at 4 and 8 weeks postoperatively. 36
Supplementary Figure S1. SEM image and pore size distribution of PLGA microspheres 38
Supplementary Figure S2. SEM image and pore size distribution of hydroxyapatite nanoparticles (nHAps) 38
Supplementary Figure S3. Surgical procedure for creating an 8 mm cranial defect in rat and implantation of the scaffold at the calvarial defect site. 40
Supplementary Figure S1. Micro-CT imaging procedures to detectbone regeneration 41
LIST OF TABLES
Table1. Sample abbreviations used in this study 30
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dc.format.extentv, 43-
dc.language.isoeng-
dc.publisher서울대학교 대학원-
dc.subjectBone regeneration-
dc.subjectSequential release-
dc.subjectCritical bone defect-
dc.subjectBone morphogenetic protein 2-
dc.subjectAlendronate-
dc.subjectNano-hydroxyapatite nanoparticle-
dc.subjectCollagen Scaffold-
dc.subject.ddc610-
dc.titleSequential dual-drug delivery of BMP-2 and alendronate from hydroxyapatite-collagen scaffolds for enhanced bone regeneration-
dc.title.alternative효과적인 골재생을 위한 hydroxyapatite-collagen 스케폴드를 이용한 BMP-2 와 alendronate 의 순차적 이중 약물 전달-
dc.typeThesis-
dc.typeDissertation-
dc.contributor.AlternativeAuthor매이단강오보이-
dc.contributor.department의과대학 의학과-
dc.description.degreeDoctor-
dc.date.awarded2021-02-
dc.contributor.major성형외과전공-
dc.identifier.uciI804:11032-000000165523-
dc.identifier.holdings000000000044▲000000000050▲000000165523▲-
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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