Mechanical deformation in living tissues generates electrical cues through ion transport, yet conventional bioelectronic interfaces remain poorly matched to soft, hydrated environments. Piezoionic materials offer a compliant alternative by converting deformation into electrical signals through mechanically perturbed electrochemical potentials and coupled ion-solvent transport rather than lattice polarization. This review examines the physicochemical basis of piezoionic transduction and multiscale strategies spanning ion-polymer interactions, nanoconfined channels, structural gradients, and electrode interfaces. These designs regulate ion selectivity, transport kinetics, electrical output, and energy conversion, enabling physiological sensing, multimodal perception, energy harvesting, and therapeutic intervention. Reported outputs span millivolts to hundreds of millivolts and nanoamperes to milliamperes, and have activated peripheral and autonomic nerves, driven electrochemical drug release, and supported cartilage, bone, and wound repair in vivo. Unstable output and the unquantified dose reaching tissue remain the principal obstacles to clinical devices that integrate diagnosis and therapy.

Myocardial infarction causes structural damage that impairs both the mechanical and electrophysiological functions of the heart. Modulating the mechanical and electrical properties of biomaterials represents a promising strategy for myocardial repair. This review systematically outlines the mechanisms and design principles of such regulation through three integrated approaches: mechanical modulation, electrical modulation, and mechano-electrical coordination. Mechanically, tuning stiffness, elasticity, and anisotropy enhances cellular alignment, tissue integration, and structural support. Electrically, regulating conductivity and anisotropy facilitates synchronous signal propagation and functional restoration. The coordinated strategy enables synergistic optimization of mechanical and electrical properties, thereby improving repair outcomes. Furthermore, biomimetic in vitro models, including cardiac organoids and heart-on-a-chip systems, provide physiologically relevant platforms for evaluating material performance. This review provides foundational insights and design principles for advancing myocardial repair via mechano-electrical biomaterial engineering.