- 期刊
化學氣相沈積法製備功能性之馬來醯亞胺基生醫鍍膜
Vapor-Based Synthesis of Maleimide- Functionalized Biomedical Coating
摘要
本研究利用化學氣相沉積聚合法由馬來醯亞胺基對二甲苯二聚體(4-N-maleimidomethyl[2,2]paracyclophane)成功地製備出具有馬來醯亞胺基的聚對二甲苯鍍膜(poly[(4-N-maleimidomethyl- p-xylylene)-co-(p-xylylene)])，可適用於各種基材並易於溫和之反應條件下進行硫醇基-馬來醯亞胺基的耦合反應(thiol-maleimide coupling reaction)。此鍍膜技術之應用將著重於其抑制蛋白質吸附以及控制內皮細胞成長之效果。表面之＂雙點擊＂反應將在溫和且不需使用催化劑的條件下經由azide-alkyne click reaction與thiol-maleimide coupling reaction分別固定螢光標定之azides以及cystines來展示其可行性，且不發生交叉反應(cross-reaction)。最後，此一多組成表面將展示不同之生物功能，包括下列理念：i)藉由azide-alkyne click reaction polyethylene glycols(PEGs)固定於整個基材表面，以保持背景之低結垢 (low-fouling state) 特 性；ii) 經由 thiol-maleimide coupling reaction 固定具有生物活性之分子以啟動表面之生物活性。 此外，細胞培養測試於心臟支架 (stent) 基材上進行，首先以其中一個官能基固定能提供表面低結垢狀態(low-fouling state)之polyethylene glycols來抑制非預期之干擾，同時接上Cys- Arg-Glu-Asp-Val (CREDV)胜肽序列展現其生物活性，最後於此基材上進行 human umbilical vein endothelial cells (HUVECs)之細胞貼附測試。
並列摘要
The first maleimide-functionalized poly-p-xylylene is synthesized via chemical vapor deposition (CVD) polymerization from 4-N-maleimidomethyl-[2,2]paracyclophane on various substrates. Coated substrates are readily available to perform thiol–maleimide click reaction under mild conditions. Designed surfaces are highlighted in low-protein-fouling modification as well as manipulated attachments and growth of bovine arterial endothelial cells. The availability of the maleimide functionality is further exploited in combination with alkynyl moiety, and the direct synthesis to prepare the multicomponent coating containing the two functionalities is enabled via CVD copolymerization on various substrates. The novel coating is comprised of distinguished anchoring sites of electron-deficient alkynes and unsaturated maleimides and is readily to simultaneously proceed doubled ＂click＂ reactions. XPS and IRRAS characterizations have verified the chemical composition for the coatings. The demonstration of synergically doubled bioorthogonal reactions is performed via azide-alkyne click reaction and thiol-maleimide coupling reaction to immobilize fluorescently labeled azides and cystines, respectively, under mild conditions in water and without the need of a catalyst, and no trace of cross-reaction is found. Finally, the multicomponent surface is designed to exhibit distinct biological functions by first immobilizing polyethylene glycols that provide a low-fouling state (bioinert) to suppress undesired background perturbance, while at the same time, addressing surface bioactive function is performed by tethering Cys-Arg-Glu-Asp- Val (CREDV) peptides on stent substrate and the adhesion of human umbilical vein endothelial cells (HUVECs) are precisely manipulated.