In Situ Monitoring and Electrical Modulation of Cellular Behaviors Directly at the Cell–Electrode Interface

Electrical stimulation (ES) can modulate diverse cellular responses, offering promising applications in cell biology, regenerative medicine, and tissue engineering. Although extensive studies explore ES effects, understanding the cell-electrode interface, where cells directly interact with electrical cues, remains challenging. This study presents a platform for investigating ES effects on cellular behaviors at this interface. The platform employs biocompatible, conductive, and optically transparent indium tin oxide (ITO) thin films to enable in situ monitoring and electrical modulation of cellular responses. The platform allows for real-time monitoring of ES-mediated dynamics, including in vitro migration and angiogenesis in ex vivo tissues, which is challenging to achieve with conventional metal electrodes. The ITO configuration is optimized using finite element analysis and direct electric field measurements to provide uniform electrical cues. Under modest voltage (<1.00 V), diverse cellular behaviors in vitro are visualized, including proliferation, migration, and angiogenesis. Optimal ES conditions for specific responses are highly cell-type dependent. Additionally, the platform demonstrates the potential for exploring ES effects at the tissue-electrode interface using mouse metatarsal tissue as an ex vivo model. This multidisciplinary study advances insights into ES and its effectiveness in biological systems by integrating bioelectronic interface engineering, bio-functional analysis, and numerical simulations.