Designing Viscoelastic Bioelectronic Interfaces: From the Organ to Cell Scale

Abstract

Living tissues are non-linearly elastic materials that exhibit viscoelasticity and plasticity. Man-made, implantable bioelectronic arrays mainly rely on thin films of ductile metals encapsulated by rigid plastic or hydrophobic elastic materials. Despite reliable electrical recordings in these arrays, the materials composition mismatch between the device and the tissue can lead to a poor interface. Further, the electrode-tissue interface is also limited, as the structure of metals is very different from the native extracellular architecture. In this thesis, I introduce tissue-like materials which can improve the material-biological interface from the organ to cell scale. First, I engineer a surface microelectrode array that replaces both the traditional encapsulation and conductive components with viscoelastic materials. The entirely viscoelastic array overcomes previous limitations in matching the stiffness and relaxation behavior of soft biological tissues by using hydrogels as the outer layers. Next, I introduce a novel hydrogel-based conductor made from an ionically conductive alginate matrix enhanced with carbon nanomaterials (e.g. graphene, carbon nanotubes). These high aspect ratio additives provide electrical percolation even at low loading fractions, and I fabricate ultra-soft viscoelastic conductive electrodes and electrical tracks that intimately conform to convoluted organ surfaces, such as the heart or the brain. This combination of conducting and insulating viscoelastic materials, with top-down manufacturing, allows for the versatile fabrication of electrode arrays compatible with in vivo recording and stimulation. I further developed the viscoelastic electronics to fabricate biomaterial scaffolds that can support the growth and network formation of neuronal cells. These ‘biohybrid electronics’ are viscoelastic with a storage modulus kPa, and tunable parameters (e.g. pore size, stiffness, viscoelasticity, additive(s) and concentration(s)). Various neuronal cell types, including neural progenitor cells are viable in the scaffolds for more than 12 weeks, and form networks around the porous structures. I quantify the density of network formations and assess the differentiation of neural progenitor cells into neurons and glial cells, including astrocytes and oligodendrocytes. Finally, I describe an electrical stimulation set-up which can direct the migration and orientation of cells that are in the scaffolds. The tunability and simplicity of the viscoelastic bioelectronic platform may overcome many of the challenges in accessing cortical regions, such as within the sulci, and enable improved in vitro platforms for tissue engineering. With the ability to design substrate and electronics components with predefined mechanical, electrical, and chemical properties, our approach can be easily used to investigate a variety of biological systems from development to disease progression and investigate potential therapies.