摘要:表面黏附的細菌,在植入性生醫元件以及材料的使用上,常常是造成這些元件以 及材料失去功能的主要原因,也因此衍生出各種臨床醫療行為複雜的問題,導致醫療 資源的浪費。儘管在抗菌材料的研究領域如此蓬勃發展,仍然很少有特定的材料能夠 有效的和持續的表現阻抗細菌黏附的特性。主要挑戰包括:缺乏以材料表面分子的化 學組成為出發點來了解的阻抗細菌黏附的機制;現有的研究也僅限於控制材料表面的 單一功能特性,例如:單方面地降低蛋白質吸附或僅僅研究如何阻抗已成形(後期) 的細菌族群。在此研究計畫中,我們的目標是利用先進的聚合物技術,來改變基質材 料的表面特性,如表面化學,拓撲結構,形態和親疏水性,以及梯度(gradient)的表 現,從而獨立評估其對細菌黏附作用的影響。此研究計畫的核心技術是根據我們研究 團隊先前開發的官能性聚對二甲苯(functionalized poly-p-xylylenes)為藍本,並採 用化學氣相沈積聚法(CVD polymerization)來製備此多功能性高分子鍍膜。透過此 鍍膜改質技術可精確地將上述表面特性呈現於所研究的基底上,並以基因定序的方法 來建立系統化的細菌族群生長變異資料庫。我們將以大腸桿菌為實驗模型,並系統化 地研究上述各種基材表面特性對大腸桿菌的黏附作用的交互影響。具體目標如下:
1) 對基材表面的特性進行系統化的表面特性設計並透過鍍膜技術來達到性能控 制,如表面化學,拓撲結構,表面形貌,親疏水性和梯度的表現。
2) 研究上述各種基材表面特性對大腸桿菌的黏附機制的影響,研究重點在細胞外 纖維(如 curli)在初期細菌族群生長的表現。
3) 使用商用的大腸桿菌基因芯片來鑑定上述各種基材表面特性對細胞生長途徑 的影響。
此研究計畫以表面分子設計為出發點來進行阻抗細菌黏附的研究,並期盼將能解 決許多臨床的複雜問題,例如:多功能鍍膜修飾後的導管可以解決臨床上因為細菌引 起的傳染性疾病,如導管相關性尿路感染。此計畫所開發的先進表面改質技術將有助 於未來生醫鍍膜,仿生技術以及生物界面工程的發展。
Abstract: Adhesion of bacteria to implanted biomaterials is a leading cause of device malfunction and clinical complications. As a consequence, bacteria-based infections attribute to a substantial part of health-related costs. In spite of the intense research in the area of bacterial-resistant materials, there are very few materials that show effective and sustained bacterial resistance. Major challenges include the lack of understanding of the molecular aspects that render a surface bacterial-resistant, and the focus on single-function materials, e.i. chemistries that only reduce protein adsorption or only target late-state bacteria colonization.
In this proposed project, we aim to use advanced polymer technology to deconvolute critical of the substratum, such as surface chemistry, topology, morphology, and wettability, thereby enabling independent assessment of their role for bacterial adhesion. The surface modification technology used in this proposal is based on our recently developed biomedical coatings based on a novel class of vapor-deposited polymers: functionalized poly-p-xylylenes. The herein proposed technology will further identify necessary specifications for the CVD copolymerization, while demonstrating the fundamental feasibility of multi-functional coatings. Moreover, the CVD-based coatings can be generically applied to a wide variety of substrates – including polymer, such as PTFE, stainless steel, Nitinol, and tungsten being the most common materials used in cardiovascular implants. The modified substrata will finally be used to establish a series of genetically defined bacteria strains. We will study the role of substratum-related factors on initial Escherichia coli (E. coli) adhesion. The specific objectives are as follows:
1) Synthesis and characterization of designer substrata with independently controllable properties, such as surface chemistries, topologies, morphologies, wettability, and gradients.
2) Study of the interaction of E. coli with a library of designer substrata prepared in task (1), with a specific focus on the role of extracellular fibers (e.g. curli) on the initial surface colonization.
3) Identification of cellular pathways that are triggered by E. coli binding to the designer substrata from task (1) using commercially available E. coli gene chips.
Those molecularly design surfaces will be of significant clinical relevance, as they will lead to multi-functional catheter coatings to address the clinical problem of bacteria-caused infectious diseases, such as catheter-associated urinary tract infections. Future advances in these areas will not only contribute to the advancement of biomedical coatings, but also stimulate further scientific and technological progress in biointerface engineering.