Xianchi Zhou, Zihao Zhu, Wenbin Dai, Wenzhong Cao, Zuolong Liu, Kexin Chen, Yan Yu, Fan Zhang, Shaomin Zhang, Fan Jia, Youxiang Wang, Jian Ji, Peng Zhang
Tissue-electronic interfaces are vital for neural implants, health monitoring devices, and augmented reality applications; however, the host immune reaction against the electrodes profoundly impacts their durability, precision, and overall fidelity. Building a highly immunocompatible yet conductive interface for implantable electrodes remains a significant challenge. Here, by screening PEDOT derivatives functionalized with diverse immunoregulatory moieties, we identified PEDOT-TMO as a candidate combining superior immunocompatibility with robust conductivity for long-term bioelectronic implants. PEDOT-TMO/PSS coatings exhibit substantially mitigated acute inflammation and chronic fibrotic response following subcutaneous implantation in mice compared to conventional PEDOT/PSS, while preserving its original electrochemical properties. During extended in vivo brain implantation trials in freely moving rat models, we observed that the immunocompatible conductive polymer-coated silicon electrode can reliably record electrophysiological signals for at least 8 weeks, demonstrating significantly better performance compared to PEDOT/PSS-coated and bare electrodes. Notably, the PEDOT-TMO/PSS interface substantially reduced the expression of S100A9 in surrounding brain tissue. Pharmacological inhibition of S100A9 similarly attenuated tissue responses to brain implants, suggesting a target for neuroinflammation inhibition. The new type of immunocompatible conductive polymer reported here holds promise in enhancing and extending the long-term function in a range of bioelectronic devices by attenuating local immune responses to functional bioelectrodes.