Large-scale manufacturing engineered 3D cardiac spheroids for dynamic electrophysiological biosensing and precise...

Cardiovascular disease remains a leading cause of mortality worldwide. Three-dimensional cardiac models hold great promise to study disease mechanisms and develop new therapies. In this work, we establish a 3D cardiac spheroids biosensing platform that integrates large-scale 3D cardiac spheroids preparation and dynamic electrophysiological recording. Cardiac spheroids are cultured for consecutive days to optimize their robust self-assembly and uniform morphology. The optimal cardiac spheroids exhibit rhythmic electrical and mechanical signals, indicating functional maturation and biomimetic replication of cardiac electromechanical properties. Moreover, the cardiac spheroids models could precisely assess the norepinephrine administration, revealing the positive regulatory mechanisms of β1-AR signaling and GRK/β-arrestin-mediated negative feedback in 3D cardiac spheroids. RNA sequencing further highlights the advantages of 3D cardiac spheroids over 2D monolayer cultures and validates the underlying mechanisms of drugs. The developed cardiac spheroids biosensing platform serves as a powerful and scalable tool for cardiac tissue modeling, functional assessment, and pharmacological evaluation.