設計合成含雙硫鍵之氧化還原響應型交聯劑分子及生物可降解雙離子性水膠之製備與應用相

Redox Thiol-Stimuli Zwitterionic Hydrogel

周大詮(CHOU,TA-CHUAN)

指導教授 ： 周崇榮

中原大學/工學院/化學工程研究所/碩士(2019年)

https://doi.org/10.6840/cycu201900680

摘要

本研究描述了由親核性加成反應製備具有氧化還原響應性的交聯劑Cystamine-co-GMA(CG4)，並且以此交聯劑與SBMA單體合成具有生物降解性的雙離子水膠。此設計具有良好抗蛋白質貼附能力與血液相容性良好的生物相容性，並且藉由交聯劑的氧化還原響應性可以使水膠具備部分降解的功能改變水膠內部網目的大小。此研究重點在於響應性降解材料的開發，期望在受到響應性導致部分降解後生物相容性與其抗蛋白質沾黏的能力並不會受到影響。
本研究對合成出來的氧化還原型響應性交聯劑(CG4)使用NMR做化學性質的檢測，之後對合成出具有氧化還原響應性與生物降解性的水膠(CG4-SBMA hydrogel)進行降解測試，並利用掃描式電子顯微鏡、接觸角量測儀、Ellman's Method檢測其降解過後的物理及化學性質；並在檢測降解後的血液相容性上，進行了人體血纖維蛋白原貼附、溶血測試、活化血小板貼附等實驗，證明了降解後的水膠仍然具有良好的血液相容性。此外藉由包覆標準蛋白進行蛋白質釋放實驗，結果顯示藉由氧化還原響應性交聯劑(CG4)所合成出的水膠的確具有蛋白質緩釋的潛力。

關鍵字

響應性 ； 氧化還原 ； 生物降解性 ； 雙離子 ； 抗沾黏 ； 水膠 ； 硫醇

並列摘要

Stimuli-responsive has an important part in the study of the smart materials. Redox-responsive and biodegradable crosslinking reagent (Cystamine-co-GMA, CG4) based on Glycidyl methacrylate (GMA) and cystamine was synthesized using nucleophilic epoxy-amine chemistry. To further investigate this crosslinker, hydrogel was fabricated by CG4 and zwitterionic monomer (Sulfobetain methacrylate, SBMA) for potential sustained protein-releasing carrier. Whereas CG4 provides hydrogel biodegradability, degradation of CG4 did not adversely affect the biocompatibile properties of the hydrogel. After degradation by treatment of dithiothreitol (DTT) at various concentrations, the mesh size of hydrogel increased from 12nm to 22nm in the study. Furthermore, in vitro studies also confirmed the blood of the degraded hydrogel, which was demonstrated by human fibrinogen adhesion, hemolysis test, and activated platelet adhesion. Subsequently in protein-releasing experiment, the trend in the early stage was consistent with the trend of mesh size expansion of the degraded hydrogel calculated by the theoretical model. CG4 represents a promising material system as a biomedical and smart material for an important part of partially degradable materials.

並列關鍵字

Zwitterionic ； Hydrogel ； Redox ； Responsive ； biodegradable ； anti-fouling ； thiol

參考文獻

1. Ratner, B. D., Biomaterials ScienceI: An introduction to materials in medicine CHAPTER I.1.6 ROLE OF WATER IN BIOMATERIALS. In Biomaterials Science, 2013; pp 55-59.

2. Vogler, E. A., Structure and reactivity of water at biomaterial surfaces. Advances in colloid and interface science 1998, 74 (1-3), 69-117.

3. Bag, M. A.; Valenzuela, L. M., Impact of the Hydration States of Polymers on Their Hemocompatibility for Medical Applications: A Review. Int J Mol Sci 2017, 18 (8), 1422.

4. Chen, S.; Li, L.; Zhao, C.; Zheng, J., Surface hydration: Principles and applications toward low-fouling/nonfouling biomaterials. Polymer 2010, 51 (23), 5283-5293.

5. Tsuruta, T., On the role of water molecules in the interface between biological systems and polymers. Journal of Biomaterials Science, Polymer Edition 2010, 21 (14), 1831-1848.