Building Hybrid Technology Platforms to Mimic the Nervous System

Biomaterial scaffolds have emerged as a tool to build 3D cultures of cells which better resemble biological systems, while advancements in bioelectronics have enabled the modulation of cell proliferation, differentiation, and migration. Here, we first describe a porous conductive hydrogel with the same mechanical modulus and viscoelasticity as neural tissue. Electrical conductivity is achieved by incorporating low amounts (<0.3% weight) of carbon nanomaterials in an alginate hydrogel matrix, and then freeze-drying to introduce a highly porous network. The mechanical and electrical properties of the material can be carefully tuned and used to modulate the growth and differentiation of neural progenitor cells (NPCs). In addition to forming neurite networks that span the material in 3D, the NPCs can differentiate into astrocytes and oligodendrocytes. With increasing hydrogel viscoelasticity and conductivity, we observe the formation of denser neurite networks and a higher degree of myelination. Application of exogenous electrical stimulation can then be applied to the scaffolds to further promote NPC differentiation. To investigate the functionality of neurite networks in 3D, we begin by placing a polydimethylsiloxane (PDMS) microstructure on an underlying multielectrode array (MEA), as previously described. We then explore different materials and techniques to integrate hydrogels into the PDMS microstructures, such that the hydrogel can facilitate neurons to form 3D networks while still confined by the PDMS. This platform is compatible with various methods to assess neuronal functionality (e.g. MEA electrical recordings), and can be used to understand the effect(s) of hydrogel properties on the resulting neuronal networks. Both described biomaterial platforms can support the growth of neuronal cells for over 100 days, and could facilitate the development of biohybrid electronic devices to understand neuronal development and disease.