Amine plasma-modified PCL surfaces for Naproxen immobilization and release for restoring osteogenic differentiation of LPS-stimulated MC3T3-E1 cells = 아민 플라즈마 개질을 통한 PCL 표면의 나프록센 고정화 및 방출에 의한 LPS-자극 MC3T3-E1 세포의 골분화 회복에 관한 연구

다국어 초록 (Multilingual Abstract)

Inflammation is a critical factor that impairs bone regeneration by suppressing the osteogenic activity of preosteoblastic cells. To address this, this study establishes a plasma-mediated surface engineering strategy to sequester and subsequently release naproxen (a nonsteroidal anti- inflammatory drug) from a poly(ε-caprolactone) (PCL) film surface, thereby restoring osteogenic differentiation under inflammatory conditions. Amine plasma polymerization introduced positively charged amine functional groups onto the PCL surface, which enabled electrostatic immobilization of the carboxylate-bearing naproxen molecules thereon. Electrokinetic analysis, atomic force microscopy, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and water contact angle measurements of the PCL surface confirmed the successful incorporation of amine groups and subsequent drug attachment. The amine plasma surface-modified PCL films exhibited markedly increased hydrophilicity and demonstrated a characteristic two-phase naproxen release profile under physiological conditions, characterized by a rapid initial discharge succeeded by a continuous and extended elution period. In vitro studies using lipopolysaccharide (LPS)-stimulated MC3T3-E1 preosteoblastic cells demonstrated that the plasma-modified, naproxen- loaded PCL film surface maintained excellent cytocompatibility. Importantly, naproxen released from the functionalized surface moderately reduced the secretion of pro-inflammatory cytokines, specifically interleukin-1 beta (IL- 1β) and interleukin-6 (IL-6), thereby alleviating inflammation-induced suppression of osteogenic differentiation. Consequently, alkaline phosphatase (ALP) activity and the expression of osteogenic marker genes RUNX2, alkaline phosphatase, and osteopontin were significantly restored compared with unmodified controls. Taken together, the results suggest that amine plasma treatment offers a robust strategy for anchoring anti-inflammatory agents onto biodegradable matrices and regulating their subsequent elution. This engineered system exhibits a twofold therapeutic capability by mitigating pro-inflammatory pathways while simultaneously reinstating osteogenic differentiation, thereby demonstrating its applicability as an effective biomaterial for bone tissue engineering in inflamed microenvironments.

목차 (Table of Contents)

• Content
• List of Figures ⅲ
• List of tables Ⅵ
• Abstract Ⅶ
• 1. INTRODUCTION 1
• 2. ACADEMIC BACKGROUND 5
• 2.1. Principles of Plasma Surface Modification 5
• 2.2. Mechanism of Electrostatic Drug Immobilization and Controlled
• Release 9
• 2.3. Mechanism of LPS-Induced Inflammation Signaling in Osteoblastic
• Cells 9
• 2.4. Molecular Regulation of Osteogenic Differentiation and Its Recovery
• under Inflammation Conditions 12
• 3. MATERIALS AND METHODS 14
• 3.1. Materials 14
• 3.2. Amine Plasma Polymerization 14
• 3.3. Surface Characterization 15
• 3.4. Naproxen Immobilization and Release 16
• 3.5. In vitro Evaluation 16
• 3.6. Statistical Analysis 18
• 4. RESULTS 19
• 4.1. Surface characterization 19
• 4.2. Naproxen Immobilization and Release Kinetics 30
• 4.2.1. Quantification of Immobilized Naproxen 30
• 4.2.2. Naproxen Release Kinetics 30
• 4.3. In vitro Study 35
• 4.3.1. Cell Viability 35
• 4.3.2. Anti-Inflammation Effect 37
• 4.3.3. Restoration of Osteogenic Activity by Naproxen Under Inflammation
• Conditions 41
• 5. DISCUSSION 44
• 6. CONCLUSIONS 47
• References 49
• 국문 초록 59