Advanced Mechano-Electrical Coupling Biomaterials for Orthopedics: From Fundamental Mechanisms to Clinical Translation.

Musculoskeletal tissues are continuously subjected to mechanical stimulation during physiological activity, accompanied by the generation of endogenous bioelectrical signals. Such mechano-electrical coupling plays a pivotal role in tissue development, homeostasis, and repair. However, injury or pathological conditions often disrupt or weaken the local bioelectrical microenvironment, thereby limiting regenerative outcomes. Driven by the need to reconstruct the electrophysiological microenvironment, mechano-electrical coupling strategies based on piezoelectric, triboelectric, magnetoelectric, and piezoionic mechanisms have emerged as a promising approach for orthopedic biomaterials. These strategies move biomaterials beyond passive structural support, enabling them to function as intelligent, self-powered bioelectronic interfaces. By converting physiological motion, ultrasound, or external mechanical loading into localized and rhythmic electrical cues, these platforms can regulate cellular behavior and reshape the tissue microenvironment. This review summarizes the major sources of mechanical forces and their mechano-electrical transduction pathways, introduces representative mechano-electrical material and platform strategies, and highlights their major applications in orthopedic regeneration and disease treatment. It also discusses key challenges in mechanistic understanding, stimulation parameter optimization, biosafety, and clinical translation, and outlines future prospects for intelligent electricity-generating biomaterials and self-powered bioelectronic systems in orthopedic therapy.