COMBINATORIAL DEVELOPMENT OF NANOSTRUCTURED MATERIAL LIBRARIES FOR THE STUDY OF CELL SUBSTRATE INTERACTION

An in vivo cellular microenvironment in which cells are immobilized contribute an essential role in diverse cellular behavior, consisting of cellular morphology, dynamics and eventually cellular fate. Micro and nanofabrication tools widely used to mimic the in vivo surrounding to manipulate cellular microenvironment for elucidating underlying mechanisms of cellular processes. Following this concept, nanostructured (ns) material gradients and material libraries were developed in order to gain an insight of cell behavior on engineered substrates comprising nanotopography. This thesis highlights the development of gradients of nanostructured titania thin films attributing different roughness without influencing the chemical nature in order to understand the physical cues regulating primary cellular activities including proliferation and differentiation. The surface topographies were characterized by atomic force microscopy (AFM), chemical composition by energy dispersive X-ray spectroscopy (EDS) and wettability was investigated by contact angle measurements. PC12 cells derived from a Pheochromocytoma of the rat adrenal medulla were cultured on five different morphologies in presence of nerve growth factor (NGF) and the results suggest that the increasing roughness not only diminishes cellular attachment but also reduces the probability of differentiation and formation of focal adhesions. The second phase of the work targets the development of nanostructured material libraries for studying PC12 cell adhesion and growth. Here we described a combinatorial approach to construct libraries of metals comprising 54 physicochemical combinations induced by surface chemistry and topography. In addition the surface properties including surface topography, surface chemistry, and wettability were characterized followed by investigating cellular behavior influenced by different physicochemical conditions of nanostructured material libraries.