Department of Biochemistry and Molecular Biology, University of Ferrara, Via F. Mortara 74, Ferrara, 44121, Italy.
Lab Chip. 2011 May 21;11(10):1776-85. doi: 10.1039/c1lc20082h. Epub 2011 Apr 6.
This paper describes a method for the production of alginate microfibres using glass-based microfluidic chips fabricated by a photolithography-wet etching procedure. The main focus of the work is the fabrication of a cell containing multifunctional microfibres which have great potential for applications in drug release formulations and tissue engineering scaffolds (to guide the regeneration of tissues in predefined sizes and shapes) providing cell structural support and immunoisolation. The key parameters, which critically influence the formation of microfibres and their geometries, were identified by a classical intuitive approach COST (Changing One Separate factor a Time). In particular, their effects on the microfibre diameter were investigated, which are directly associated with their functionalities relating to the implantation site, the nutrient availability and diffusion/transport of oxygen, essential nutrients, growth factors, metabolic waste and secretory products. The interplay between the alginate solution concentration, pumping rate and gelling bath concentration in controlling the diameter of the produced microfibres was investigated with a statistical approach by means of a "design of the experiments" (DoEs) optimization and screening. Finally, the processing impacts on cell viability, the cellular effect of wall thickness consistency and the spatial distribution of cells within the alginate microfibre were examined. We provide an approach for the production of alginate microfibres with controlled shape and content, which could be further developed for scaling up and working towards FDA approval.
本文介绍了一种使用基于玻璃的微流控芯片生产藻酸盐微纤维的方法，该芯片通过光刻-湿法刻蚀工艺制造。这项工作的主要重点是制造包含多功能微纤维的细胞，这些微纤维在药物释放制剂和组织工程支架（用于引导组织在预定大小和形状中再生，提供细胞结构支撑和免疫隔离）中有很大的应用潜力。通过经典的直观方法 COST（逐个改变一个因素）确定了关键参数，这些参数对微纤维的形成及其几何形状有很大的影响。特别是，研究了它们对微纤维直径的影响，这与它们与植入部位、营养物质的可用性以及氧气、必需营养物质、生长因子、代谢废物和分泌产物的扩散/传输有关的功能直接相关。通过“实验设计”（DoE）优化和筛选的统计方法，研究了藻酸盐溶液浓度、泵送率和凝胶浴浓度在控制所生产的微纤维直径方面的相互作用。最后，研究了处理对细胞活力的影响、壁厚度一致性的细胞作用以及细胞在藻酸盐微纤维内的空间分布。我们提供了一种具有可控形状和含量的藻酸盐微纤维生产方法，该方法可以进一步开发，以实现规模扩大并朝着 FDA 批准的方向发展。
