Zwitterionic Hydrogel Design of PEDOT:PSS Suppresses The Foreign Body Response against Bioelectronic Conductors

Implantable medical devices (IMDs) are playing an increasingly important role due to an aging population and the associated increasing prevalence of chronic diseases. However, the foreign body response (FBR) has limited IMDs from realizing their full potential. The FBR is characterized by inflammatory and fibrotic processes that surround the implanted material. Degradative chemicals and enzymes produced in the process can damage the implant. Fibrotic encapsulation is particularly detrimental for biosensors and electrophysiological devices because it would impede the diffusion of analytes and ions. A class of materials with promising FBR suppressing properties are zwitterionic polymers which have been shown to nearly eliminate the FBR for at least a year in mice. As electronic materials for IMDs, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is of interest because it is chemically stable, highly processable, non-cytotoxic, and has good mixed ion-electron conducting properties. Nonetheless, previous work addressing the FBR against PEDOT:PSS did not place their focus on long-term solutions or did not carry out FBR-specific characterization methods. We hypothesize that by combining PEDOT:PSS and a zwitterionic polymer into a double-network hydrogel and carefully tuning its phase separation morphology, the conductivity can be increased and the FBR can be suppressed indefinitely. In this work, we demonstrate a process for inducing PEDOT:PSS network formation <i>in situ</i> in a zwitterionic hydrogel matrix, which significantly improves its conductivity and reduces FBR-associated fibrosis. Our work demonstrates that controlling the phase separation morphology of composite materials can be an effective strategy for suppressing the FBR.