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Surface Modification of Biomaterials using Zwitterionic Polymers for Anti-calcification
- 주제(키워드) surface modification , zwitterion , anti-fouling , anti-calcification
- 발행기관 아주대학교
- 지도교수 박기동
- 발행년도 2020
- 학위수여년월 2020. 2
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000029771
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Calcification is one of the major issues in the field of implantable medical devices which reduces their function and lifetime. The calcification process on the surface of the devices is largely divided into two stages. The initial stage is the formation of calcium complexes due to various biological and artificial factors, and the final stage is the non specific adsorption of the resulting calcium complexes onto the surface Several methods have been studied to interfere with the crystallization phase of calcium. However, due to the diverse mechanisms by which crystals are formed, calcium deposition cannot be completely prevented. Therefore, there is a need for a method that results in minimal calcium deposits on the surface. The surface treatment strategy to prevent this adsorption mainly uses the anti-fouling properties. It has been reported that hydrated surfaces using various kinds of hydrophilic materials exhibited anti-fouling properties. Many studies suggested that zwitterionic molecules have high anti-fouling properties due to their strong electrostatically induced hydration effect. In this study, various strategies were used to confirm the anti-calcification ability by surface modification of zwitterionic polymers. We synthesized phenol-conjugated zwitterionic poly (sulfobetaine methacrylate-co-tyramine) (pSBTA) and PEG type polymers with different end group charges. The polymers were characterized by 1H NMR and UV-Vis spectroscopy to confirm the conjugation of TA groups. Then the polymers were grafted onto surfaces via tyrosinase (Tyr)-catalyzed reaction which can be used to modify phenolic moieties in mild environments with fast reaction rates and on regardless of the type of substrates. Optimized grafting conditions for each type were set (pSBTA : 2.5 wt%, 0.4 kU/mL) (PEG types : 2.5 wt%, 0.8 kU/mL). The immobilization of pSBTA was confirmed by measuring static water contact angle and X ray p hotoelectron s pectroscopy (XPS). In PU-pSBTA, contact angle degree was decreased compared with bare-PU and XPS revealed new picks were confirmed at 167 eV in the S 2p region and 401 eV in the N 1s region compared to the Bare PU. The in vitro (7 days) and in vivo (4 weeks) anti-calcification effects of bare-PU and PU-pSBTA were analyzed by ICP. The amounts of calcium measured in vitro were decreased from 10.6 to 4.2 μg/cm2 compared to bare-PU. In vivo, it decreased from 75.6 to 45.6 μg/cm2. These developed functional surfaces with anti-calcification property could be expected as promising materials for various biomaterial implants.
more목차
I. INTRODUCTION 1
1. Calcification of implantable devices 1
2. Strategies for anti-calcification surfaces 3
2.1 . Metal ion coated surface 3
2.2 . Drug r eleas ing s urface 3
2.3 . Surfac e topography 4
2.4 . Anti fouling surface 4
3. Design of anti-fouling surfaces 5
3.1. Strategies for anti-fouling surfaces 5
3.1.1. Neutralization of surface charge 5
3.1.2. Hydration 6
3.1.3. Steric repulsion 6
3.2. Development of anti-fouling polymers 8
3.2.1. Poly (ethylene glycol) PEG based polymer 8
3.2.2. Zwitterionic based polymer 9
3.2 2.1. Phosphobetaine 9
3.2.2.2. Carboxybetaine (CB) 9
3.2.2.3. Sulfobetaine (SB) 10
4. Tyrosinase-mediated surface modification 11
5. Overall objectives 13
II. Materials and Methods 14
1. Materials 14
2. Synthesis of sample polymers 14
3. Characterization of sample polymers 17
3.1. Nuclear magnetic resonance (NMR) 17
3.2. UV-Vis spectrometer 17
4. Preparation of polymer grafted surfaces 18
4.1. Optimization of grafting conditions 18
5. Surface characterization of pSBTA-grafted on PU surfaces 19
5.1. Static water contact angle measurement 19
5.2. X-ray photoelectron spectroscopy (XPS) 19
5.3. Atomic force microscopy (AFM) 19
5.4. Ellipsometer 20
6. Evaluation of anti-calcification properties 20
6.1. In vitro simulated body fluids model (SBF) 20
6.2. In vivo mouse subcutaneous implant model 21
III. RESULTS AND DISCUSSION 22
1. Synthesis and characterization of sample polymers 22
1.1. Nuclear magnetic resonance (NMR) 22
1.2. UV-Vis spectrometer 22
2. Preparation of polymer grafted surfaces 23
2.1. Optimization of grafting conditions 23
3. Characterization of pSBTA-grafted surfaces 28
3.1. Static water contact angle measurement 28
3.2. X-ray Photoelectron Spectroscopy (XPS) 28
3.3. Atomic force microscopy (AFM) 29
3.4. Ellipsometer 31
4. Evaluation of anti-calcification properties 32
4.1. In vitro simulated body fluids model (SBF) 32
4.2. In vivo mouse subcutaneous implant model 33
IV. CONCLUSION 35
REFERENCES 36
