Developing Multifunctional Hydrogels with Tissue-Like Properties for Improved Cell-Material Interfaces

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 (&lt;0.3% weight) of carbon nanomaterials in an alginate hydrogel matrix, and then freeze-drying to self-organize into highly porous networks. 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). With increasing hydrogel viscoelasticity and conductivity, we observe the formation of denser neurite networks and a higher degree of myelination. Similarly, fibroblasts can be incorporated into the scaffolds and cell migration can be modulated through the application of exogenous electrical stimulation, for applications to wound healing. To investigate the functionality of neural systems, both <i>in vitro </i>and <i>in vivo </i>platforms can be realized. By placing a polydimethylsiloxane (PDMS) microstructure on an underlying multielectrode array (MEA), we can then explore different materials and techniques to integrate hydrogels into the PDMS microstructures and can facilitate the growth of neuronal networks in 3D. Additionally, implantable surface electrode arrays can be fabricated, with the ability to record from the brain and heart with enhanced tissue conformability and minimal damage to the biological organs. The described biomaterial platforms can be used to investigate neuronal development and disease progression.