Microelectrodes enable dynamic biointerfaces for closed-loop organs-on-chips

Organs-on-chips (OoCs) have emerged as a revolutionary toolbox to replicate the in vivo microenvironment and simulate the key functions of human tissues and organs. These systems offer a promising alternative to animal models in disease modeling, drug screening, and personalized medicine. A key limitation of conventional OoCs, however, is their inability to capture and respond to bioelectrical signals, hindering elucidation of dynamic (patho)physiological processes. Moreover, most OoCs with integrated microelectrode sensors operate in an open-loop configuration, lacking actuation mechanisms to modulate these processes guided by real-time monitoring and biofeedback. Herein, we explore the diverse applications of integrated microelectrode sensors within OoCs and identify both technical challenges and emerging opportunities. We discuss the state-of-the-art progress in electrode materials and sensor designs that enable the closed-loop framework in OoC systems, thus creating real-time sensing/monitoring, stimulation, and therapeutic interventions. These closed-loop systems promise to unlock new possibilities in adaptive drug delivery, responsive tissue engineering, and precision medicine. Ultimately, we emphasize that a holistic, system-level design approach, rather than a sole focus on electrode performance, is crucial to advancing the next generation of microelectrode-integrated closed-loop OoCs.