Harnessing piezoelectricity for musculoskeletal regeneration: microcurrents to tissue repair

Piezoelectric scaffolds are emerging as promising therapeutic strategies for musculoskeletal regeneration. These materials convert mechanical forces, ranging from intrinsic motion to focused ultrasound (US) force, into localized electrical cues for tissue-specific musculoskeletal regeneration. Mechanistically, piezoelectric-converted electrical energy activates mechanosensitive and voltage-gated channels that trigger early regenerative signaling pathways. In this review, we describe the fundamental principles of the piezoelectric material class that focus on dipole alignment, geometry, and activation paradigms to culminate in their differential effects on the regeneration of musculoskeletal tissues. We also discuss lead-free platforms, closed-loop systems, as well as printable constructs capable of delivering wire-free electrical stimulation (ES). Finally, we discuss current translational challenges and future directions and practical steps toward clinical adoption of piezoelectric scaffolds.