Zwitterionic hydrogel designs for conducting polymers enable bioelectronics with suppressed foreign body response

For long-term, continuous operation of implantable biosensors and electrophysiological devices, the foreign body response (FBR) is a major obstacle that needs to be overcome. As the FBR progresses, any implanted device will become damaged and isolated from its physiological environment, due to encapsulation by fibrotic tissue and inflammatory immune cells. To achieve more compatible and low-impedance biointerfaces, conducting polymers, such as PEDOT:PSS, have been extensively explored as ideal materials. However, FBR on such conducting polymers remains an unmet challenge. We report a zwitteronic-hydrogel-based double-network design for PEDOT:PSS that can significantly suppress the FBR by 64%, in addition to improving conductivity by more than one order of magnitude. Surprisingly, the FBR level of this design is even lower than that of the parent zwitteronic hydrogel by 53%. Our further immunological investigations at the histological, cellular, and transcriptomic levels give deeper insights into the unique effects that come from the chemical heterogeneity. Furthermore, chronic electrocardiographic recording in mice demonstrate the benefit of this material design to long-term, implanted electrophysiology, which provides indications for the future development of immunocompatible electronic polymers.