製備具高血液相容性之表面接枝雙離子性刷狀高分子

Preparation of Highly Hemocompatible Surface-Grafted Zwitterionic Polysulfobetaine Brushes

羅珮慈(Pei-Tzu Lou)

指導教授 ： 張雍

中原大學/工學院/化學工程研究所/碩士(2013年)

https://doi.org/10.6840/cycu201300862

摘要

現階段生醫材料的發展重點之一，是在於如何控制該材料微結構界面與人體組織或血液接觸時，能夠具有良好的生物相容性。本研究設計並發展一種簡易的表面雙離子化(surface zwitterionization)改質方法，期以強化生醫材料之血液相容性質。首先，以矽晶圓基材為理想研究模型，將該表面產生高密度之雙鍵官能基，經由熱誘導表面起始聚合將雙離子性硫代甜菜鹼 (sulfobetaine methacrylate, SBMA)單體接枝於基材表面，並藉由改變單體濃度，來調控雙離子性刷狀高分子之接枝鏈段長。研究過程中，以表面接觸角量測儀及X射線光電子能譜儀，確認改質後基材表面之物理與化學性質，並使用專一性酵素連結免疫吸附法量測人體纖維蛋白質於其表面的吸附性質，以建立雙離子化接枝密度與蛋白質吸附間之關聯性。經由血小板活化與血球貼附實驗，來評估雙離子化材料界面之血液相容性質。最後，於聚四氟乙烯 (Poly(tetrafluoroethylene); PTFE), 聚偏二氟乙烯 (Polyvinylidene fluoride; PVDF), 聚丙烯 (Polypropylene; PP), 氧化鋁(Al2O3), 醫療級鈦金屬(Ti)與醫療級不銹鋼(SUS316L)等六種不同的材料表面上進行修飾，以驗證此一表面雙離子化改質方法使用於高分子、陶瓷、以及金屬材料的通用性。

關鍵字

雙離子 ； 血液相容性

並列摘要

This work describes the design and preparation of well-hemocompatible biomaterials used in contact with human blood. A simple and convenient method of preparing a hempcompatible zwitterionic polysulfobetaine methacrylate (polySBMA) surface was employed in this study. Silicon wafer (Si wafer), a well-known biomaterial, was used as the model ceramic material to investigate the effect of zwitterionic surface coverage with human blood compatibility. Si wafer was first coupled with organosilane initiator to form a stable silanization layer which was further grafted with poly(SBMA) polymers via thermal polymerization approach. The grafting coverage of zwitterionic polySBMA brushes was controlled through varying the SBMA monomer concentration. The physical and chemical properties of polySBMA-grafted Si wafer were characterized by water contact angle measurement (CA) and X-ray photoelectron spectroscopy (XPS). The blood compatibility of polySBMA-grafted surfaces was evaluated by assessing the adhesions of blood platelets and erythrocytes on the substrate surfaces using scanning electron microcopy (SEM) and confocal laser scanning microscopy (CLSM). The level of protein adsorption was also determined by an enzyme-linked immunosorbent assay (ELISA) to establish the relationship between polySBMA grafting coverage and protein adsorption. This surface modification method was further employed on various polymeric, ceramic and metal biomaterial surfaces, eg. poly(tetrafluoroethylene) (PTFE), polyvinylidene fluoride (PVDF), polypropylene (PP), aluminium oxide (Al2O3), titanium (Ti), and 316L type stainless steel (SUS316L). Results show that thermal polymerization is an effective and versatile method of grafting zwitterionic polySBMA brushes on a wide range of biomaterials.

並列關鍵字

zwitterionic ； hemocompatibility

參考文獻

1. Georgiev, G.S., et al., Self-Assembly, Antipolyelectrolyte Effect, and Nonbiofouling Properties of Polyzwitterions. Biomacromolecules, 2006. 7(4): p. 1329-1334.

2. S. J. Singer, G.L.N., fluid mosaic model of cell membranes. 1970.

3. Lewis, A.L., Phosphorylcholine-based polymers and their use in the prevention of biofouling. Colloids and Surfaces B: Biointerfaces, 2000. 18(3–4): p. 261-275.

5. Ishihara, K., et al., Effects of phospholipid adsorption on nonthrombogenicity of polymer with phospholipid polar group. Journal of Biomedical Materials Research, 1993. 27(10): p. 1309-1314.

6. Nam, K.W., J. Watanabe, and K. Ishihara, Characterization of the Spontaneously Forming Hydrogels Composed of Water-Soluble Phospholipid Polymers. Biomacromolecules, 2002. 3(1): p. 100-105.