3D 프린팅을 이용한 항생제 방출 식도 패치의 조직 재생 효과에 대한 연구

학위논문(박사) -- 서울대학교대학원 : 의과대학 의학과, 2021.8. 정은재.Esophageal defects can cause exposure of the fistula site to various bacterial species, which could lead to a severe inflammatory response. We designed and manufactured a 3D-printed patch consisting of a lattice pattern and thin-film with biodegradable polycaprolactone (PCL), that released the antibiotic, tetracycline (TCN). We reconstructed an artificial defect in the rat esophagus using this patch. The efficacy and availability of 3D-printed antibiotic-releasing patches were evaluated using both quantitative and qualitative assessment methods. PCL was used to print the lattice pattern on a pre-manufactured thin film with approximately 100μm resolution, which had been mixed with tetracycline (TCN) at 100°C and 1000°C to release the antibiotic evenly. In vitro tests showed that TCN was released for more than 1 month. In addition, in vitro cytotoxicity test demonstrated excellent cell compatibility. 3D-printed antibiotic-releasing patches were applied on the defect sites after creating artificial partial esophageal defects in rats. Four weeks after the surgery, leakage was checked using micro-computed tomography with an oral contrast agent injected into the rat mouth. No leakage was evident in any part of the esophagus. For analyzing tissue regeneration, immunohistochemistry was performed. M1 and M2 macrophage activation was verified by immunohistochemistry of CD-68 and CD-163. Desmin immunohistochemistry showed significant muscle layer regeneration in the TCN (1% and 3%) patch groups. Moreover, sufficient re-epithelialization and neo-vascularization were affirmed in TCN (1% and 3%) patch groups. In this study, we confirmed that 3D-printed antibiotic-releasing patches not only have anti-microbial effects but also have tissue regeneration ability in the area surrounding the esophageal fistula site. The results of this study can be applied in further studies on tissue-engineering.식도 결손은 결손부에 대한 다양한 세균총에 대한 노출을 유발하며, 이는 심한 염증 반응을 유발한다고 알려져 있다. 저자 및 연구진은 생분해성 polycaprolactone (PCL)을 사용하여 3D 프린터로 격자 모양 및 박막으로 구성된 패치를 제작하였고, 여기에 항생제, tetracycline (TCN)이 방출될 수 있도록 하여 인공적으로 만든 식도 결손에 대한 재건을 시도하였다. 이후 정성적, 정량적 분석을 통해 패치의 활용도와 효능을 평가하였다. PCL은 미리 작업된 박막 위에 100 μm 해상도의 격자 모양으로 3D 프린팅 하였으며, 100°C에서 녹인 TCN와 PCL 입자를 혼합하여 3D 프린팅 함으로써 TCN이 패치에서 방출될 수 있도록 하였다. 체외실험에서 TCN 은 1달 이상 지속적으로 방출되는 것을 확인할 수 있었으며, 또한 세포독성에 대한 체외실험에서 패치 추출물이 뛰어난 세포적합성을 보임을 확인할 수 있었다. 이후 쥐에서 부분 식도결손을 유발한 후 제작된 패치를 적용하였고 3주 후 micro CT를 이용해 누출 여부를 확인하였다. 쥐의 구강을 통해 조영제를 주사하여 확인한 결과 모든 패치 이식군에서 식도 전장에 누출은 관찰되지 않았다. 수술 후 4주 및 12주에 각각의 군을 희생하여 조직학적 재생 정도를 확인한 결과, 1% 와 3% TCN 패치 그룹에서 유의미한 근육층 재생이 관찰되었고, 면역조직화학염색 분석 결과, 1% 및 3% TCN 패치 그룹에서 재 상피화 및 이식부위 주변 신생혈관 생성이 잘 이루어진 것을 확인할 수 있었다. 본 연구에서는 3D 프린팅을 이용한 항생제 방출 패치를 활용하였을 때, TCN의 항균 효과와 더불어 누공 주위에 식도 근육층을 비롯한 조직 재생에도 충분한 효과가 있음을 확인하였으며 이는 추후의 연구에서 매우 활용성이 높을 것으로 생각된다.Chapter 1. Introduction 1 Chapter 2. Materials and Methods 4 Chapter 3. Results 15 Chapter 4. Discussion 24 Chapter 5. Conclusion 29 Tables and Figures 30 Bibliography 59 Abstract in Korean 64박

구강편평세포암에서 암줄기세포표시인자(CD24,44,133)과 수술 후 예후의 관계 분석

학위논문 (석사)-- 서울대학교 대학원 의과대학 의학과, 2017. 8. 안순현.Introduction: Many studies have focused on the prognostic roles of cancer stem cell markers, but the results remain unclear. CD44 is the most well-known cancer stem cell marker in head and neck cancers, and CD24 and CD133 are representative cancer stem cell markers in many solid tumors. The aim of this study was to gain insight into the relationships between expression of CD24, CD44, and CD133, either alone or in combination, and prognostic parameters of oral squamous cell carcinoma (OSCC). Methods: Patients with OSCC who underwent successful surgical resection from January 2003 to December 2011 in a single tertiary hospital were included in this study. Tissue arrays composed of 67 primary tumor tissues were generated and used for immunohistochemistry (IHC) against CD24, CD44, and CD133. IHC was graded by a semiquantitative histologic scoring system (H score) that considered the extent and intensity of the staining. IHC results were correlated with clinicopathological characteristics and with clinical outcomes such as relapse-free, disease-free, and overall survivals. Results: In the 67 cases, the oral tongue was the most frequently affected primary site (56.7%). In tumor-lymph node-metastasis (TNM) staging, stage IV (34.3%) was most frequent, followed by stages I (26.9%), II (25.4%), and III (13.4%). Despite successful resection, there was 28.3% recurrence. TNM stage IV was highly related with the recurrence rate (p = 0.002). None of the 3 cancer stem cell markers (CD24, CD44, and CD133) had a statistically significant relationship with lymph node metastasis, TNM stage, or microscopic invasion into adjacent tissues. High expression of CD44 alone was associated with relapse-free survival (p=0.049), as were combined high expression of CD44 and CD133 (p=0.046) and CD44 and CD24 (p=0.015). CD44 expression also tended towards correlation with disease-free survivalhowever, this was not statistically significant (p=0.071). Conclusions: Overall, the expression of CD44 had the strongest correlation with tumor recurrence. Additionally, when CD44 expression was combined with CD24 expression, CD24+CD44+ patients had the poorest chance of relapse-free survival. Thus, CD44 expression alone, and also in combination with CD24, should be considered when evaluating the prognosis for relapse-free survival of OSCC.I. Introduction 1 II. Materials and Methods 2 III. Results 6 IV. Discussion 10 V. Conclusion 15 VI. References 37 VII. Abstract in Korean 41Maste

한-EU, 한-미 무역구조 비교분석

학위논문 (석사)-- 서울대학교 대학원 : 국제학과(국제지역학전공), 2011.2. 문우식.Maste

건식에칭이 퍼말로이 (Ni81Fe19) 박막의 자기적 특성에 미치는 영향

Thesis (doctoral)--서울대학교 대학원 :금속공학과,1998.Docto

Maximum entropy model-based intra-sentence segmentation for efficient syntactic analysis

학위논문(박사)--서울대학교 대학원 :컴퓨터공학과,1999.Docto