Biological response to structured and functionalized substrates for nerve tissue regeneration

Abstract

After a lesion in the CNS, glial cells play a fundamental role, being the mediators of both the inhibitory and the beneficial response for neural regeneration. The tissue engineering approach consists in the use of biomaterials to help the regeneration and guide the regenerative capable cells to create a permissive environment. The main working hypothesis of this thesis is that we can promote a favourable environment for CNS regeneration identifying material properties which can modulate neuronal cells behaviour. In a first place we analyzed glial and neuronal response to two very different biopolymers, PMMA and chitosan. Wettability, surface and mechanical properties were characterized for both materials. Then line pattern of different dimensions in the micrometrical range were introduced. The response of glial cell and neurons were analyzed in terms of cell adhesion, morphology and differentiation state. Finally, we studied the behaviour of glial cells on glass model surfaces functionalized by self assembling monolayers with different wettability (OH, COOH, NH2, CH3), in order to identify the specific role that wettability plays in determining cell response. The dates suggest that the adhesion, the morphology and the differentiation state of neuron and glial cells can be controlled by choosing the proper combination of material properties and physical patterns. Overall, line patterns resulted to be a suitable tool to use in biomaterial design for nerve regeneration. However, the performance of each material must be analyzed with attention, since the combination of material properties, which most of the time is not predictable, play important roles in the biological activity.