Development of electroconductive mats to direct neural cell growth and maturation.

Nowadays, the fast development of manufactural technologies and high demand of new drugs and therapeutics, make more and more essential a step forward for cell culture systems and organ and tissue in vitro models. Indeed, current preclinical models such as animals or 2D cell cultures are poor predictors of the tested drug’s effect in humans. The differences in the great part of human physiological tissues structures compared to animals and the over-simplified model lacking all the main features of in vivo microenvironment in the case of 2D models, have brought the scientific community to ask for more representative and precise models in order to obtain more reliable results while reducing laboratory animal testing according with the 3R principles. Currently, advanced in vitro cell cultures and translational approaches such as microfluidic systems and 3D scaffold-based models are leading the new frontiers of in vitro models, as they are becoming necessary to better understand certain mechanics and biophysical behaviour that cells and tissues show in vivo, even though their deployment is still limited to toxicology and basic research. Focusing on the human central nervous system, neural tissue is characterized by an inherent complexity both in terms of composition and structural properties. Thus, in order to get closer to recreate the in vivo neural microenvironment and its dynamic interaction with cells, it’s impossible to ignore the several stimuli that neural cells undergo. For this reason, a multi-stimuli integrated approach is required to try to emulate such a complicated system. In this work, electroconductive PCL-PANI nanofibrous mats have been developed, possessing a specific aligned architecture and high biocompatibility to act as a substrate for neural cell culture. NE-4C cells, a progenitor lineage capable to differentiate into neurons and astrocytes, have been employed for in vitro assays. The main stimuli offered by the topography and the electroconductivity given by PANI, have been demonstrated to have a marked influence on directing and promoting NE-4C growth and maturation. The final idea is to incorporate these culture substrates in a new prototype of bioreactor provided by IVTech which will furtherly integrate a 3D dynamic culture conjugated with an exogenous electrical stimulation to finally evaluate the effect that these stimuli have over the cells and, in particular, if they work synergistically. Incorporating physiologically relevant stimulation in a controlled environment allows the neural stem cell populations to differentiate and maturate in a heterogeneous and functional tissue in terms of morphology and marker expression. This aims to be a first step toward developing a family of next-generation in vitro models, that consist in fully functional, high-throughput platforms, as advanced tools for scientific neural research and drug discovery.