Effect of Topography, Stiffness and Biochemicals on Neuronal Differentiation

Abstract

The mechanical and biochemical modifications of the hydrogel substrates play an essential role in tissue engineering research and neurodegenerative therapies. Topography, stiffness, and biochemicals are known to have important influences on neural cells, such as cell adhesion, proliferation, migration, and differentiation. These factors not only affect cells independently but also have a combined effect. The purpose of this thesis is to investigate these impacts on neural cells. We first hypothesized that topography and stiffness would affect neuronal differentiation and maturation. Polyacrylamide hydrogels were used to provide promising scaffolds for human neural progenitor cells (hNPCs) attachment. Both healthy hNPCs and Rett-syndrome disease hNPCs were used to examine the cell behaviors on different combinations of topographies and stiffnesses. Then healthy hNPCs were cultured for 21 days to assess the effects on neuronal differentiation and maturation. Next, we hypothesized that topography and biochemicals would impact cell adhesion and differentiation. With biocompatibility and biodegradability properties, polyvinyl alcohol (PVA) hydrogels are considered a great resource for regenerative medicine. However, the plain PVA surface rarely supports cell attachment. The biochemical modifications are necessary for further cell studies. PC12 cell lines were used to study the cell adhesion, proliferation, and viability on various biochemical conjugation. Then PC12 cell lines were seeded on the PVA substrates with different topographies and biochemicals to study the combined effect on cell differentiation and the neurite length. Overall, the findings of this research work show the specific combinations of mechanical and biochemical modifications would promote cell adhesion and differentiation.