치료 기능 부가를 위한 이식형 의료기기의 표면 코팅 연구

학위논문 (박사)-- 서울대학교 대학원 : 협동과정 바이오엔지니어링전공, 2015. 2. 최영빈.This dissertation is described with material, design, fabrication and analysis/evaluation for surface coating of implantable medical devices, i.e., bone fixation systems and silicone implants, in order to add the therapeutic functionality. Even though the implantable medical devices have been widely developed and used in the clinical field, these still have drawbacks associated with lack of therapeutic functionality. To solve these, we suggest a promising multifunctional medical device adding therapeutic functionality, maintaining intact functionality of the implantable medical device. Firstly, in order to control the corrosion rate of magnesium (Mg), we coated the surface of magnesium (Mg) with a biodegradable polymer, polycaprolactone (PCL) and varied coating thickness in a reproducible manner using an automated apparatus designed to follow the widely-accepted dip-coating method. Herein, PCL served as a good permeation barrier owing to its hydrophobicity and slower degradation in biological fluid than Mg. As we increased the coating thickness from 0 to 13.31 ± 0.36 µm, the volume of hydrogen gas and amount of Mg ions, the indicators of Mg corrosion, decreased by almost half from 0.57 ml/cm2/day and 0.55 mg/day to 0.20 ml/cm2/day and 0.26 mg/day, respectively. Therefore, we demonstrated that the thicker coating could better hinder the water permeation to the Mg surface and thus, a corrosion rate could be reduced in this work. Secondly, we prepared a bone plate enabled with local, sustained release of alendronate, which is a drug known to inhibit osteoclast-mediated bone resorption and also expedite bone-remodeling activity of osteoblasts. For this, we coated a bone plate already in clinical use (PLT-1031, Inion, Finland) with a blend of alendronate and a biocompatible polymer, azidobenzoic acid-modified chitosan (i.e., Az-CH) photo-crosslinked by UV irradiation. As we performed the in vitro drug release study, the drug was released from the coating at a rate of 4.03 μg/day for 63 days in a sustained manner. To examine the effect on bone regeneration, the plate was fixed on an 8 mm cranial critical size defect in living rats and a newly formed bone volume was quantitatively evaluated by micro-computed tomography (micro-CT) at schedule times for 8 weeks. At 8 week, the group implanted with the plate enabled with sustained delivery of alendronate showed a significantly higher volume of newly formed bone (52.78 ± 6.84 %) than the groups implanted with the plates without drug (23.6 ± 3.81 %) (p < 0.05). The plate enabled with alendronate delivery also exhibited good biocompatibility on H&E staining, which was comparable to the Inion plate already in clinical use. Therefore, we suggest that a bone plate enabled with local, sustained delivery of alendronate can be a promising system of a combined functionality of bone fixation and its expedited repair. Lastly, we proposed the acute, local suppression of transforming growth factor beta (TGF-ß), a major profibrotic cytokine, to reduce fibrosis around silicone implants. To this end, we prepared silicone implants that were able to release tranilast, a TGF-ß inhibitor, in a sustained manner for 5 days or 15 days. We performed histologic and immunohistochemical analyses for 12 weeks after the implantation of the implants in living rats. The capsule thicknesses and collagen densities significantly decreased compared with those around the non-treated silicone implants. Notably, early suppression of TGF-ß affected the fibrogenesis that actually occurs at the late stage of wound healing. This change may be ascribed to the decrease in monocyte recruitment mediated by early TGF-ß during the acute inflammatory reaction. Thus, a significant decrease in differentiated macrophages was observed along with a decrease in the quantity of TGF-ß and fibroblasts during the subsequent inflammation stagethese changes led to a diminished fibrotic capsule formation.Abstract ⅰ Contents v List of Tables ix List of Figures xi Chapter 1. Introduction 1 1.1 Implantable Medical Devices 1 1.2 Bone Fixation system 7 1.2.1 Drawbacks of Bone Fixation system 12 1.3 Silicone Implant 16 1.3.1 Drawbacks of Silicone Implant 23 1.4 Research Purpose 28 Chapter 2. Surface Coating of Implantable Medical Devices 30 2.1 Surface Coating Technology 30 2.1.1 Dip Coating 31 2.1.2 Spray Coating 34 2.1.3 Drop Casting 37 2.2 Biopolymers as a Coating Material 39 2.2.1 Synthetic polymer: Polycaprolatone(PCL) and Poly(lactic-co-glycolic acid)(PLGA) 44 2.2.2 Natural polymer: Chitosan 53 Chapter 3. Polycaprolactone Coating with Varying Thicknesses for Controlled Corrosion of Magnesium 60 3.1 Introduction 60 3.2 Materials and Methods 64 3.2.1 Materials 64 3.2.2 Sample Preparation and Coating Process 65 3.2.3 Immersion test 66 3.2.4 Characterization of PCL coating 67 3.3 Results 68 3.3.1 Coating analysis 68 3.3.2 Coating Rate Analysis 69 3.3.3 Surface Characterization during Corrosionl 71 3.4 Discussion 73 3.5 Conclusion 76 Chapter 4. Acute Suppression of TGF- ß with Local, Sustained Release of Tranilast against the Foramtion of Fibrous Capsules around Silicone Implants 90 4.1 Introduction 90 4.2 Materials and Methods 94 4.2.1 Materials 94 4.2.2 Sample Prepartion 95 4.2.3 Characterization 96 4.2.4 In vivo Animal Study 98 4.2.5 Histopatholoic Evaluation by Various Stainging Methods 99 4.2.6 Statistical Analysis 100 4.3 Results 101 4.3.1 Implant Characterization 101 4.3.2 Capsule Thickness 103 4.3.3 Collagen Density 105 4.3.4 Fibroblasts 106 4.3.5 TGF-ß 107 4.3.6 Monocytes/macrophages 109 4.4 Discussion 110 4.5 Conclusion 113 Chapter 5. Bioabsorabable Bone Plates Enabled with Local, Sustained Delivery of Alendronate for Bone Regeneration 149 5.1 Introduction 149 5.2 Materials and Methods 153 5.2.1 Materials 153 5.2.2 Synthesis of an Aziobenzoic Acid-Modified Chitosan (Az-CH) 154 5.2.3 Preparation of Bone Plate Samples 154 5.2.4 Characterizations of Az-CH 156 5.2.5 Characterizations of Az-CH 157 5.2.6 Measurement of Drug-Loading Amount 157 5.2.7 Measurement of Drug-Loading Amount 158 5.2.8 In vivo Drug Release Study 159 5.2.9 In vivo Cell Cytotoxicity Evaluation 159 5.2.10 In vivo Animal Study 160 5.2.11 Histopathologic Evaluation 162 5.2.12 Statistics 163 5.3 Results 163 5.3.1 Characterization of Az-CH 163 5.3.2 Characterization of Plate Samples 164 5.3.3 In vitro Drug Release Profile 166 5.3.4 Cytotoxicity 166 5.3.5 In vivo new bone formation 167 5.3.6 Histological Evaluation 168 5.4 Discussion 168 5.5 Conclusion 171 Chapter 6. General Conclusion 186 References 189 Abstract in Korean 199 Acknowledgement 202 Appendix 204Docto

수소가 2차원 그래핀, 그래핀산화물, 이황화몰리브데늄의 전기적 특성에 주는 영향

학위논문 (박사)-- 서울대학교 대학원 : 융합과학부, 2017. 2. 박영우.Two-dimensional(2D) materials have attracted great scientific attention due to their extraordinary and fascinating properties. Graphene and transition metal dichalcogenides such as MoS2, have shown promising candidate for gas sensing, flexible electronics, energy harvesting due to their high mechanical properties, high surface-to-volume ratio, low noise and sensitivity of electronic properties to the changes in the surroundings. It has been intensively investigated on the interaction between hydrogen and 2D materials both experimentally and theoretically. Therefore, it is required that studies of the interaction between hydrogen and 2D materials have been increasingly required due to the indispensable modification of the electronic structure of 2D materials for device applications and the possibility of using 2D materials as hydrogen storage materials. In this dissertation, we will describe the effect hydrogen on the electronic properties of 2D materials such as Graphene, Graphene Oxide, MoS2 using electrical conductivity, thermoelectric power (TEP), and Raman spectroscopy. The first part of this thesis describes presenting a simple method to fabricate p-n junction in a single layer graphene by means of the selective H2 exposure. This is achieved by the fabrication of poly methyl methacrylate (PMMA) window on the half region of the graphene. The gate voltage (VG)- dependent resistance of single layer graphene is measured as a function of H2 (12 bar) exposure time at 350 K. As hydrogen exposed sample, n-doping of the window region shifts to the negative VG region prominently compared with that of the PMMA-covered region. The temporal evolution of Dirac point both PMMA region and window region follows first order Langmuir adsorption model. Consequently, a single graphene p-n junction is obtained by measuring the VG-dependent resistance of the whole graphene region. The second part of this thesis describe the electrical transport properties of single layer reduced graphene oxide(RGO) and its hydrogenation. The single layer RGO is obtained by bubble deposition method and thermal reduction. The structure and reduction efficiency is confirmed by X-ray photoelectron spectroscopy and Raman spectroscopy, respectively. The RGO contains 82 % of C=C and C-C species and have 2 nm of defect distance. The transfer characteristic of RGO shows ambipolar transport for temperature range (10 K 70 K), the charge transport become 2D-VRH due to absence of coulomb gap. The ES-VRH is additionally confirmed by electric field dependent conductance of non-Ohmic regime at low temperature. The TEP exhibits that the dominant charge carrier in RGO is switched at charge neutrality point. The Seebeck coefficient is proportional to T1/3 (50 K < T < 300 K) suggesting a 2D VRH conduction. Hydrogenation of RGO shows n-type doing resulting from hydrogen adsorption. Maximum resistance of transfer curve is reduced by improvement of reduction efficiency. The third part of this thesis will introduce the effect of hydrogen on geometric and electronic structure of single layer MoS2. MoS2 is well known catalyst for hydrodesulfurization process and the hydrogen adsorbed plays an important role in its activation. So that, investigations of the interaction between molecular hydrogen and molybdenum disulfide have been increasingly demanded for the understanding of the HDS process, especially the hydrogen adsorption on MoS2 and creation of sulfur vacancies in MoS2. Electrical transport properties were measured as a function of time at 350 K and 12 bar of hydrogen atmosphere. Upon to hydrogen exposure, the threshold voltage of MoS2 is shifted toward negative bias, which indicates n-type doing by thiol bonding and sulfur vacancy. The temporal evolution of threshold voltage follows double exponential first adsorption model, which consist of thiol bonding term and sulfur vacancy term. The mobility has increase as exposure to hydrogen, which result from screening of long range scatterer by intercalated hydrogen between MoS2 and substrate. The n-type doping of MoS2 by hydrogen is confirmed by TEP measurement. The TEP curve is shifted toward negative gate bias region likewise transfer characteristics. We observe the red shift of the two prominent peaks in Raman spectroscopy by electron doping and strain.Chapter 1. Research background 1 1.1 2D Materials 1 1.1.1 Graphene 2 1.1.2 Graphene Oxide 4 1.1.3 MoS2 5 1.2 Raman Spectroscopy 7 1.2.1 Raman Spectroscopy of graphene and graphene oxide 7 1.2.2 Raman Spectroscopy of MoS2 9 1.3 Variable range hopping theory 12 1.4 Thermoelectric power 14 Chapter 2. Formation of graphene p-n junction by selective hydrogen adsorption 21 2.1 Introduction 21 2.2 Experimental details 22 2.3 Result and discussion 24 2.3.1 Transfer characteristics 24 2.3.2 Raman spectroscopy 30 2.4 Summary 31 Chapter 3. Electrical transport of reduced single layer graphene oxide and its hydrogenation 35 3.1 Introduction 35 3.2 Experimental details 36 3.2.1 Synthesis of graphene oxide 36 3.2.2 Preparation of single layer reduced graphene oxide 37 3.2.3 Transport properties measurement 39 3.3 Characterization (AFM, Raman, XPS) 39 3.4 Result and discussion 42 3.4.1 Temperature dependence of conductance 42 3.4.2 Thermoelectric power 48 3.5 Hydrogenation 51 3.6 Summary 52 Chapter 4. Effect of hydrogen on geometric and electronic structure of MoS2 57 4.1 Introduction 57 4.2 Experimental details 59 4.3 Result and discussion 60 4.3.1 Transfer characteristics 60 4.3.2 Mobility 62 4.3.3 Effect of sulphur vacancy and thermoelectric power 64 4.3.4 Raman spectroscopy 67 4.4 Summary 68 Chapter 5. Conclusion 73 Appendix 77 A.1 Introduction 77 A.2 Experimental details 78 A.3 Result and discussion 79 A.3.1 Temperature dependence of resistance 79 A.3.2 MR of 1T-TaS2 with CCDW state 80 A.3.3 MR of 1T-TaS2 with H state 82 A.4 Summary 83 국문 초록 87Docto

Polymeric Tube-Shaped Devices with Controlled Geometry for Programmed Drug Delivery

학위논문 (석사)-- 서울대학교 대학원 : 협동과정 바이오엔지니어링전공, 2012. 8. 최영빈.We developed a modular tube-shaped device as a proof of principle to enable programmed release of encapsulated molecules for controlled drug delivery. Each drug-delivery tube module was prepared by assembling two separate silicone tubes in series, one filled with a model compound (sodium fluorescein) and the other with a diffusional barrier material, polyethylene oxide (PEO). We varied the length of the PEO-filled tubes to control release from the drug-delivery tube devices. The onset times and periods of drug release increased with the length of the PEO tube in the drug-delivery tube device. To program drug release, therefore, we prepared devices with combinations of drug-delivery tube modules with PEO-filled tubes of different lengths. The combination of drug-delivery tubes with PEO-filled tubes each with very different lengths achieved pulsatile drug release, while a continuous drug release was realized by using a collection of PEO-filled tubes with small differences in length. We conclude that the modular combination of drug-delivery tubes, each composed of a diffusion-barrier tube of different length, demonstrates potential applications in programmed drug delivery.Contents 1. INTRODUCTION 1 2. STRATEGY 3 3. EXPERIMENTAL 7 I. Materials 7 II. Preparation of drug-delivery tubes 7 III. Scanning electron microscopy (SEM) 10 IV. Quantitative analysis of drug-loading amount 11 V. Measurement of water infiltration rate into the PEO tube 11 VI. In vitro drug release study 12 4. RESULTS 13 I. Characterization of drug-delivery tubes 13 II. Infiltration rate of water into the PEO tubes 16 III. In vitro drug release profiles 20 IV. Mathematical modeling of drug release 22 V. Pulsatile drug release from a combination of drug-delivery tube modules 23 VI. Continuous drug release from a combination of drug-delivery tube modules 26 5. DISCUSSION 30 6. CONCLUSION 34 REFERENCES 37 국문초록 40Maste

적층 및 구조적 개선에 의한 리튬 이차 전지의 전기화학적 특성변화에 관한 연구

학위논문(박사) --서울대학교 대학원 :재료공학부,2007.Docto

Diode Laser-Induced Fluorescence of argon metastable ion in ICP and argon neutral beam analysis with LIF technique

학위논문(석사) - 한국과학기술원 : 물리학과, 2007.2, [ iii, 37 p. ]아르곤 유도 결합 플라즈마(ICP)에서 이온의 가열 메카니즘 연구에 다이오드 레이저 유도 형광법이 사용되었다. 자기장이 없는 유도 결합 플라즈마에 다이오드 레이저를 사용하여 레이저 유도 형광을 관측한 것은 아직 학계에 발표되지 않았다. 아르곤 준안정상태 이온의 속도 분포 함수를 레이저 유도 형광법으로 측정하였고 이로부터 상대밀도와 온도를 구하였다. 글로벌 모델을 세워 계산한 결과와 실험을 통해 측정한 결과를 서로 비교해 봄으로써 다이오드 레이저 유도 형광법으로 측정한 상대 밀도가 신뢰성이 있음을 확인하였다. 글로벌 모델을 계산하는 과정에서 필요로 하는 전자온도와 전자밀도는 랭뮤어 프로프를 통하여 측정하였고 이 데이터들은 아주 신뢰성이 높은 것들이다. 아르곤 준안정 상태 이온의 온도는 측정 과정에서 정확한 파장 보정이 이루어지지 않아 신뢰성이 많이 떨어졌지만 대략 0.05 ~ 0.1eV 사이의 값이 측정되었다. 그리고 레이저 유도 형광법을 아르곤 중성빔 진단에 적용하였다. 색소 레이저를 사용하여 아르곤 중성빔의 유동 속도와 유량 측정을 시도하였다. 하지만 중성빔의 유량이 신호가 관측되기 위한 최소 범위에 미치지 못하였다. 현재 중성빔의 유량을 높이기 위한 개선 연구를 진행중이다.한국과학기술원 : 물리학과

고밀도 아르곤 플라즈마에서 준안정 아르곤 중성 밀도 거동에 관한 연구

학위논문(박사) - 한국과학기술원 : 물리학과, 2011.8, [ v, 59 p. ]한국과학기술원 : 물리학과

SUBSTRATE TREATMNET APPARATUS AND SUBSTRATE TREATMNET METHOD

본 발명은 기판 처리 장치 및 기판 처리 방법을 제공한다. 이 장치는 RF 전력을 공급하는 제1 전원부, 제1 전원부와 직렬 연결되는 제1 정합회로부, 진공을 형성하는 챔버부, 제 1 정합회로부와 전기적으로 연결되고 챔버부 내부에 배치되는 전극부, 전극부의 표면에 형성된 다이아몬드라이크카본층(diamond like carbon layer:DLC layer), 및 다이아몬드라이크카본(DLC) 층에서 이온이 입사하여 중성화된 중성빔을 통과시키는 중성빔 추출부를 포함한다

Anti-biological Fouling Behavior of Nanofibers on Superhydrophobic Surface

1