Electrical Signals at the Subcellular Scale: How Electroactive Materials Regulate Stem Cell Fate.

Abstract

Electroactive materials have emerged as a pioneering frontier at the convergence of regenerative medicine and biomaterials science. Unlike conventional biochemical approaches, which often lack spatiotemporal precision, electroactive materials such as conductive polymers and piezoelectric nanostructures can mimic the native electrical microenvironment of tissues. By directly modulating subcellular electrical signals, including organelle membrane potential and ion dynamics (e.g., in mitochondria and endoplasmic reticulum), these materials present a paradigm shift in controlling stem cell fate. This review begins by outlining the classification of electroactive biomaterials and their mechanisms of generating electrical signals under external stimuli, highlighting their dynamic interactions with stem cells. It subsequently explores how material-mediated electrical cues precisely modulate subcellular architecture and function, detailing key processes such as calcium oscillations regulated by membrane potential in endoplasmic reticulum and potential-dependent regulation of mitochondrial redox homeostasis. This article further systematically evaluates the role of electroactive materials in guiding stem cell differentiation and reprogramming, while surveying their emerging applications in neural, bone, and cardiac tissue regeneration. Finally, it presents current challenges such as precise organelle targeting and long-term electrical safety and suggests future directions, offering a theoretical and technological framework for developing electrically driven regenerative therapies.