목차

Chapter 1. General Introduction
1.1 Cancer Treatment and Drug Resistance 1
1.1.1 Cancer Microenvironment 1
1.1.2 Drug Resistance of Lung Carcinoma 4
1.2 Engineered 3D Tumor Microenvironment as Pre-clinical Models 8
1.2.1 Tumor Models for Pre-clinical Researches 8
1.2.2 Hydrogels as An Engineered 3D Tumor Microenvironment 11
1.2.3 Current Strategies for Hydrogel-based Tumor Model 14
1.3 Research Motivation and Approaches 16
Chapter 2. Interpenetrating Polymer Network Hydrogels as An Engineered 3D Tumor Microenvironment for Drug Screening of Lung Carcinoma
2.1 Introduction 18
2.2 Objectives 20
2.3 Experimental Section 21
2.3.1 Materials 21
2.3.2 Synthesis and Characterization of Thiolated Gelatin (GtnSH)22
2.3.3 Synthesis and Characterization of PEG-TA2 23
2.3.4 Preparation of IPN Hydrogels 23
2.3.5 Measurement of Phase Transition Time 24
2.3.6 Rheological Analysis 24
2.3.7 In Vitro Proteolytic Degradation 24
2.3.8 3D Encapsulation of Human Fibrous Sarcoma (HT1080) 25
2.3.9 Cytocompatibility and Proliferation Assay 25
2.3.10 Drug Resistance Test Using 5-FU 26
2.3.11 3D Encapsulation of Human Lung Carcinoma 26
2.3.12 Drug Resistance Test Using Gefitinib and PHA-665752 26
2.3.13 Drug Resistance Test Using Mouse Xenograft Model 27
2.3.14 Immunostaining of p-Akt 27
2.3.15 Statistical Analysis 28
2.4 Results and Discussion 29
2.4.1 Synthesis and Characterization of GtnSH and PEG-TA2 29
2.4.2 Fabrication of IPN Hydrogels and Phase Transition Time 32
2.4.3 Controllable Elastic Modulus (G’) of Hydrogels 35
2.4.4 Long-term Stable Matrices Against Proteolytic Degradation 37
2.4.5 Engineered Tumor Model Using IPN Hydrogels 39
2.4.6 Engineered Lung Carcinoma Microenvironment with Adjusted Matrix Stiffness 42
2.4.7 Drug Screening of Human Lung Carcinoma 46
2.4.8 Exploring the Resistance Mechanisms of Lung Carcinoma 50
Chapter 3. Conclusion and Future Direction