Toward Long-Term Bioelectronic Interfaces: Mechanical Compliance Meets Immunocompatibility

Achieving chronic stability in implantable bioelectronics requires more than strong initial performance. It depends on the synergistic integration of mechanical compliance, electrochemical functionality, and immunocompatibility, because failure in any dimension can lead to micromotion-induced damage, signal instability, or chronic inflammation. Here, we present a framework for engineering bioelectronic interfaces under immune surveillance by analyzing multiscale triggers of the foreign body response, including geometric intrusion, modulus mismatch, and interfacial chemistry. We evaluate representative flexible and stretchable metal-based systems that improve mechanical matching but often lack bioactive or immunomodulatory design. We then discuss conductive hydrogels as hydrated conductors that can bridge mechanical and electrochemical mismatches, while emphasizing that their host response cannot be assumed and must be engineered. Finally, we outline material-level strategies-dopant selection, network architecture, and molecular functionalization-and discuss remaining challenges in micro/nanofabrication, hybrid integration, and application-oriented molecular design.