Polymer Surfaces for Sustained Cell Growth: Development and Study of Molecular Interactions

本研究的目的是研究不同的聚合物底物对细胞行为、细胞形态、细胞结构蛋白的组织和基因表达的影响。它还将有助于理解细胞/聚合物的相互作用，以开发新的聚合物系统，用于持续的细胞生长。哺乳动物细胞在固体基质上的持续生长和功能取决于基质的理化性质。虽然这一现象的分子基础尚不清楚，但它在大规模细胞培养和人工内脏器官的发展中具有重要意义。该方法是跨学科的，涉及工程方法与生物化学和分子生物学技术的整合。独特的聚合物表面，包括可生物腐蚀的表面，将通过定制合成和超临界流体溶剂的改性而产生；这些表面将在表面化学，粗糙度和表面能方面完全表征。成纤维细胞和肝细胞将在多种聚合物表面培养。细胞行为、细胞骨架组织和特定基因表达的变化将通过定量计算机辅助显微镜和生化分析来确定。通过控制和检查从聚合物表面到细胞蛋白的几个不同水平的分子变化，底物特性的变化将与细胞功能的精确影响相关联。最后，新型底物将在不添加培养基血清补充剂的情况下提供生物重要因子的局部释放。

The objective of this research is to examine the influence of different polymeric substrates on cell behavior, cell morphology, organization of cellular structural proteins, and gene expression. It will also assist understanding cell/polymer interactions to develop novel polymeric systems for sustained cell growth. The sustained growth and function of mammalian cells on solid substrates depends on the physiochemical nature of the substrate. Although the molecular basis of this phenomenon is not well understood, it is of major importance in the development of large-scale cell culture and artificial internal organs. The approach is interdisciplinary, involving the integration of engineering methods with biochemical and molecular biology techniques. Unique polymer surfaces, including bioerodable surfaces, will be created by custom synthesis and by modification with supercritical fluid solvents; these surface will be completely characterized in terms of surface chemistry, roughness, and surface energy. Fibroblasts and hepatocytes will be cultured on a variety of polymer surfaces. Changes in cell behavior, cytoskeletal organization, and expression of specific genes in response to these surfaces will be determined by quantitative computer-assisted microscopy and biochemical analysis. By controlling and examining molecular changes at several different levels -- from the polymer surface to cellular protein -- changes in substrate properties with the precise effect on cell function will be correlated. Finally, novel substrates will then provide a local release of biologically important factors without the addition of media serum supplements,