Synthesis and Characterization of Shear-thinning Hydrogel using Tetronic-adamantane conjugate(Tet-Ada) and Poly(β-cyclodextrin) for Injectable Biomaterials
Synthesis and Characterization of Shear-thinning Hydrogel using Tetronic-adamantane conjugate(Tet-Ada) and Poly(β-cyclodextrin) for Injectable Biomaterials
- 주제(키워드) injectable biomaterials , injectable hydrogel , shear-thinning hydrogel , host-guest interaction , drug delivery
- 발행기관 아주대학교
- 지도교수 박기동
- 발행년도 2019
- 학위수여년월 2019. 2
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000028408
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Injectable biomaterials have been widely utilized for biomedical applications because their implantation into the human body is minimally invasive and the therapeutic agents can be delivered locally. Shear-thinning hydrogels are notable because of their unique property, whereby the viscosity decreases (solution) under a shear stress and recovers (gel) after the removal of the shear stress. However, as most shear-thinning hydrogels are formed by physical crosslinking, their mechanical properties are often poor. To overcome this issue, additional secondary cross-linkages, via UV-crosslinking, thiol-ene reaction, and oxidative crosslinking, are created. In this study, we developed a new shear-thinning hydrogel through host-guest interactions and thermo-gelling at 37℃ to improve the mechanical strength of shear-thinning hydrogels. Tetronic-Adamantane (Tet-Ada) and β-cyclodextrin polymers (poly(β-CD)) which can dissolve in aqueous environments were successfully synthesized. The chemical structures of the synthesized polymers were confirmed by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The hydrogels rapidly started to form via host-guest interactions between the Ada and β-CD and self-assembly of the Tet micelles at 37℃. The elastic modulus of the hydrogels was assessed by varying both, the concentrations of the polymers and the temperature. Importantly, the Tet-Ada/poly(β-CD) hydrogels showed shear-thinning behaviors and rapid recovery properties. They also exhibited the pH-responsive and long-term release of hydrophobic drug, doxorubicin (DOX). In addition, we demonstrated the biocompatibility of the hydrogels and the anticancer effect of the DOX released from the hydrogels. In conclusion, we suggest the potential usage of the Tet-Ada/poly(β-CD) hydrogels as injectable materials for various biomedical applications, including drug delivery systems.
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ABSTRACT ⅰ
CONTENTS ⅲ
LIST OF FIGURES ⅴ
LIST OF TABLES ⅷ
ABBREVIATIONS ⅸ
Ⅰ. INTRODUCTION 1
1. Injectable Biomaterials 1
1.1 Hydrogels 2
1.1.1 Strategy to form injectable hydrogels 3
1.1.2 Shear-thinning hydrogels 4
2. Cyclodextrins 5
2.1 Inclusion complexes with cyclodextrin using host-guest interactions 7
2.2 β-cyclodextrin-Adamantane complexes 8
3.Tetronic 8
4 Objectives 11
Ⅱ. EXPERIMENTS 13
1. Materials 13
2. Synthesis and characterization of Tetronic-Adamantane (Tet-Ada) 14
3. Synthesis and characterization of β-cyclodextrin polymer (poly(β-CD)) 15
4. Hydrogel formation 15
5. Characterization of Tet-Ada/poly(β-CD) hydrogels 16
5.1 Rheological characterization 16
5.2 Qualitative evaluation of hydrogel injectability 17
6. In vitro DOX release 17
7. In vitro cytotoxicity assay 17
8. Statistical analysis 19
Ⅲ. RESULTS AND DISCUSSION 20
1. Synthesis and characterization of polymers 20
2. Tet-Ada/poly(β-CD) hydrogel formation and characterization 23
2.1 Preparation of Tet-Ada/poly(β-CD) hydrogels 23
2.2 Rheological study 24
2.2.1 The controllability of mechanical properties 25
2.2.2 Shear-thinning and recovery property 27
2.3 Injectability 30
3. In vitro release profiles of DOX 31
4. Cytotoxicity of DOX-loaded Tet-Ada/poly(β-CD) hydrogels 32
Ⅳ. CONCLUSION 36
Ⅴ. REFERENCES 37
