Implanted flexible electronics reveal principles of human islet cell electrical maturation

Understanding how human pancreatic α and β cells develop functional electrical activity is critical for building transplantable islets. Here we report the first application of tissue-like, stretchable mesh electronics integrated during organogenesis of human stem cell–derived pancreatic organoids, enabling months-long, single-cell–resolved electrophysiology. This “cyborg pancreatic organoid” platform stably tracks spontaneous and hormone-stimulated electrical activities from individual SC-α/β cells throughout maturation and under daily metabolic entrainment. Long-term recordings reveal progressive reduction of basal firing and emergence of circadian oscillations in electrical waveforms, which correlate with hormone responsiveness and transcriptomic signatures of metabolic and exocytic gene networks. Moreover, integrated electrical actuators modulate hormone secretion, demonstrating bidirectional bioelectronic control. Together, these results establish a general framework for embedding electronics into developing pancreatic organoids to continuously trace and modulate functional maturation.