Tissue‐Stimulator Platform for Electrically Stimulating Pancreatic β‐Cells for Long‐Term Functional Regulation

ABSTRACT Pancreatic β‐cells regulate blood glucose levels through insulin secretion driven by complex electrophysiological activities, whereas lack of these activities hinders long‐term in vitro culture and β‐cell maturation. Electrical stimulation (E‐stim) can trigger electrical activity and provide signals to β‐cells; however, effective electrode integration with the pancreatic tissue remains a challenge for understanding the effects of E‐stim. Here, Conductive Electrode Navigating Electrical Cue to Tissue (CoNECT), a biohybrid 3D‐printed platform designed for seamless electrode‐tissue integration and uniform E‐stim delivery to individual pancreatic islets is introduced. CoNECT enhances calcium signaling, facilitates β‐cell aggregation, and preserves primary islet morphology, indicating its potential to enhance islet function by providing an optimized electrophysiological microenvironment. CoNECT also improves glucose‐stimulated insulin secretion index in stem cell‐derived β‐cells—increasing by up to fourfold (1.65 to 6.66)—indicating enhanced glucose sensitivity and maturation. These findings validate CoNECT as an advanced tissue‐stimulator platform for modulating excitable tissues, with potential applications in diabetes research and regenerative medicine.