Conductive hydrogels for next-generation bio-electronic interfaces
Keywords: Materials Science and Engineering.

The bio-electronic interface is the next frontier of a wide range of biomedical therapies, from implanted devices that therapeutically stimulate organs, to regenerative medicines that use electrical cues to guide stem cell differentiation towards target lineages. Yet, severe mismatch in mechanical properties at this interface remains a major challenge. Conventional conductors are significantly more stiff (E~ GPa) than soft tissues (E~ kPa), which can lead to inflammatory encapsulation of implants and misdirection of differentiating cells. Moreover, conventional rigid conductors cannot accommodate the dynamic motions of bodily surfaces, hindering the effective transmission of electrical signals across the bio-electronic interface. Finally, in stark contrast to the 3D nature of cell-cell and cell-environment interactions, typical electronic interfaces are planar and 2D, which not only limits the potential density of bio-electronic interactions but can also negatively impact cell fate. This dissertation will describe the progress we have made towards designing next-generation conductive materials capable of possessing tissue-level stiffness, high stretchability, and the capability to interface with biological targets in 3 dimensions. First, tissue-level stiffness is achieved by leveraging the ability of the conducting polymer PEDOT:PSS to form gel networks at remarkably low concentrations in water (1-2 wt%). Ionic additives that induce PEDOT:PSS gelation are rationally selected to manipulate both electrical conductivity and gelation kinetics. We demonstrate that slow gelation enables molding of highly conductive hydrogels with ultra-low storage moduli (~100 Pa). We further demonstrate that mechanical properties like stretchability can be orthogonally introduced through the use of interpenetrating polymer networks. As a proof of concept, we interpenetrate PEDOT:PSS gels with different formulations of covalently-crosslinked polyacrylic acid. The resulting conductive interpenetrating network (C-IPN) gels possess high conductivity (> 10 S/m), high stretchability (up to 400%) and tunable elastic moduli over 3 biologically-relevant orders of magnitude (8-374 kPa) without compromising electrical performance. Second, we leverage the rapid gelation of PEDOT:PSS in the presence of metal cations to create a novel patterning method called electro-gelation patterning, in which electrochemical oxidation of a sacrificial metal thin film in the presence of aqueous PEDOT:PSS electrolyte enables high-resolution features and conformal surface coatings. Finally, 3D interfacing capability is achieved by using PEDOT:PSS hydrogels as microgel building blocks to form granular conductive hydrogels, which combine jamming-induced elasticity with excellent shear-thinning properties. We demonstrate that granular PEDOT:PSS gels can be mixed with cells to create conductive 3D cell scaffolds, which can further be deployed via minimally invasive injection methods. Taken together, our novel strategies for designing these conductors represent significant steps towards the development of therapeutics that can harness the full potential of electrical functionality in medicine