그래핀 옥사이드 기반의 약물 전달을 통한 골형성 단백질 용량 감소 및 뼈 재생

학위논문 (석사)-- 서울대학교 대학원 : 협동과정 바이오엔지니어링전공, 2015. 8. 김병수.High doses of bone morphogenetic protein-2 (BMP-2) are required for effective bone regeneration. However, these high doses often cause undesirable adverse effects, including bone overgrowth, osteolysis, and activation of the immune response, and raise treatment costs. In an effort to reduce the BMP-2 dose to avoid or diminish side effects, we investigated whether delivery of BMP-2 using graphene oxide (GO) can reduce the BMP-2 dose for bone regeneration. Delivery of BMP-2 using GO flakes suspended in fibrin gels (GO/F) resulted in significantly greater osteogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro, and at various doses of BMP-2, significantly greater amounts of bone regeneration in mouse calvarial defects occurred than when fibrin gel (F) alone was used. A half-dose of BMP-2 delivered by GO/F resulted in bone regeneration similar to that resulting from a full dose of BMP-2 delivered by F. The enhanced bone regeneration efficacy was likely due, at least in part, to the sustained release, higher structural stability, and higher bioactivity of BMP-2 delivered by GO/F compared to BMP-2 delivered by F. Therefore, GO may be an effective carrier for BMP-2 to reduce the BMP-2 dose and avoid adverse effects.Abstract Table of contents List of figures List of tables 1. Introduction 2. Materials and methods 2.1. Cell culture 2.2. GO characterization 2.3. GO cytotoxicity assay 2.4. BMP-2 adsorption on GO 2.5. Release kinetics of BMP-2 2.6. Circular dichroism (CD) 2.7. Osteogenic differentiation of hBMMSCs in vitro 2.8. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) 2.9. Western blot assay for cell signaling 2.10. Mouse calvarial defect model for evaluating bone regeneration 2.11. In vivo bone formation 2.12. Statistical analysis 3. Results 3.1. GO characterization 3.2. Cytotoxicity of GO 3.3. BMP-2 adsorption on GO 3.4. In vitro release of BMP-2 from GO and structural stability and bioactivity of the released BMP-2 3.5. In vitro osteogenic differentiation of hBMMSCs by released BMP-2 3.6. In vivo bone formation 4. Discussion 5. Conclusions References Supplementary data S1. Supplementary data experimental S1.1. Loading efficiency and release kinetics of bone morphogenic protein (BMP)-2 with various GO conditions S1.2. The compressive elastic modulus of F and GO/F S2. Supplementary data figures S3. Supplementary data references 요약 (국문초록)Maste

Retrospective Analysis of Patients Suffering from Dementia or Mild Cognitive Impairment Treated by Collaboration between Western and Korean Medicine

Objectives: To investigate the characteristics of patients diagnosed with dementia or mild cognitive im-pairment who are treated by means of a blend between Western and Korean medicine.Methods: We searched for outpatients with dementia or mild cognitive impairment by means of a collaboration between Western and Korean medicine from August 1, 2015, to July 31, 2017, through electronic medical records in Wonkwang Hospital. The records were retrospectively analyzed according to the patients’ demographic and clinical characteristics, pathway of medical care, diagnostic tests, treatment, and medical expenses.Results: Thirteen patients were included in the analysis. Among them, six patients were diagnosed with mild cognitive impairment, five with dementia, Alzheimer's type, one patient with frontotemporal dementia, and one patient with unspecified dementia. Twelve of the thirteen patients were over 60 years of age. The number of pathways from the Dept. of Neurology to the Dept. of Neuropsychiatry of Korean Medicine was almost the same as the opposite pathway. The most used diagnostic test in Korean medicine was a neuro-psychological test such as SNSB, MMSE and GDS. In Western medicine, hematology and neuroimaging were frequently used for patients. Acupuncture in Korean medicine and medication in Western medicine were the most frequently used. In Korean medicine, uncovered service costs were much higher than covered service costs,. whereas, in Western medicine, covered service costs were higher than uncovered service costs.Conclusions: This study describes the basic characteristics of dementia and mild cognitive impairment patients treated by a collaboration between Western and Korean medicine. Based on these results, a clinical pathway of the collaborative practice system between Western and Korean medicine for de-mentia patients needs to be developed.This study was supported by Ministry of Health and Welfare of Korea (3234-302)