利用馬來酰亞胺聚對二甲苯鍍膜控制材料表面化學以及區域化特性達到對細胞分化之操控

Chemically and Topologically Controlled Cell Differentiation Based on Maleimide-Functionalized Parylene

蔡亞庭(Ya-Ting Tsai)

指導教授 ： 陳賢燁

國立臺灣大學/工學院/化學工程學研究所/碩士(2017年)

https://doi.org/10.6342/NTU201701327

摘要

藉由控制細胞貼附，可以廣泛的使細胞區域化生長，除此之外，本研究展示了通過精確定義的界面化學和空間拓撲來控制細胞增殖和分化區域化的形成。首先利用馬來酰亞胺官能化的聚對二甲苯(maleimide-functionalized parylene)塗層產生界面平台，此界面平台提供兩種反應途徑，包括馬來酰亞胺 - 硫醇偶聯反應(maleimide-thiol coupling reaction)和硫醇 - 烯酯反應(thiol-ene click reaction)，兩種反應途徑都可以用來固定特定分子（如生長因子蛋白），且都具有高反應特異性及可以在溫和條件下進行。藉由優雅地操作反應路徑，可以在塗層表面上進行成纖維細胞生長因子(FGF-2)和骨形態發生蛋白(BMP-2)的鍵結，並且使用微接觸印刷(μCP)和/或UV照射光區域改質技術，使生長因子區域化。經過修飾的界面提供化學和定位的信號，並使培養細胞於特定位置增殖（藉由FGF-2）及分化成骨（藉由BMP-2）。此技術也可以在相同界面上形成細胞增殖和成骨的協同模式，這是難以透過常規細胞貼附模式而達到的；同時此技術還具有將塗層應用於廣泛的材料、曲線和復雜生醫裝置上的多功能性，所以此技術可以擴展到其他生物材料的設計和界面的修改。

關鍵字

區域表面改質 ； 聚對二甲苯 ； 細胞增生 ； 分化成骨 ； 多功能

並列摘要

In addition to widely adopted cell pattern by controlling cell attachment, the patterned formation of cell proliferation and differentiation is demonstrated by precisely defined interface chemistry and spatial topology. The interface platform is created by using a maleimide-functionalized parylene coating, which provides two route-controlled conjugation accessibility including maleimide-thiol coupling reaction and thiol-ene click reaction, both with high reaction specificity and can proceed under mild conditions, that the coating technology is a prime tool for the immobilization of sensitive molecules, such as growth factor proteins. Conjugations of fibroblast growth factor 2 (FGF-2) and bone morphogenetic protein (BMP-2) were performed on the coating surface by elegantly manipulating the reaction routes, and the confinement of these conjugation reaction at selected areas was enabled by using microcontact printing (µCP), and/or photopatterning by UV irradiation. Such modified interface provides chemically- and topologially-defined signals for the recognition of cultured cells to proliferation (by FGF-2) and resolve osteogenesis (by BMP-2) activities and in registered locations. The reported technique additionally enabled the synergistic pattern formation of both the osteogenesis and proliferation activities in the same interface, which is difficult to perform by conventional cell attachment patterns. With also the versatility of applying the coating on a wide range of materials and on curve and complex devices, the proposed technology is extendable to other prospective biomaterials designs and materials’ interface modifications.

並列關鍵字

surface pattern ； poly-p-xylylene ； proliferation ； osteogensis ； multifunctional

參考文獻

1. Chen, C. S.; Mrksich, M.; Huang, S.; Whitesides, G. M.; Ingber, D. E., Geometric control of cell life and death. Science 1997, 276 (5317), 1425-1428.

2. Falconnet, D.; Csucs, G.; Grandin, H. M.; Textor, M., Surface engineering approaches to micropattern surfaces for cell-based assays. Biomaterials 2006, 27 (16), 3044-3063.

3. Ito, Y., Surface micropatterning to regulate cell functions. Biomaterials 1999, 20 (23), 2333-2342.

5. Guillotin, B.; Guillemot, F., Cell patterning technologies for organotypic tissue fabrication. Trends in Biotechnology 29 (4), 183-190.

6. Liu Tsang, V.; Bhatia, S. N., Three-dimensional tissue fabrication. Advanced Drug Delivery Reviews 2004, 56 (11), 1635-1647.