Ultrasound and its-activated smart biomaterials for programmable tissue regeneration

Ultrasound technology has emerged as a versatile physical stimulus in tissue engineering, facilitating the transition from static scaffolding to dynamic, remotely controlled regenerative ecosystems. This review systematically dissects the dual-mode therapeutic potential of ultrasound: direct biological actuation and material-mediated transduction. First, we elucidate the intrinsic mechanobiological effects, where acoustic radiation forces and streaming modulate cell fate-related processes through mechanotransduction pathways (e.g., Piezo1 activation) and reprogram the immune-vascular microenvironment without exogenous materials. Concurrently, we classify the evolution of ultrasound-responsive smart materials, ranging from piezoelectric nanogenerators to cavitation-sensitive carriers. Special emphasis is placed on their energy transduction mechanisms, enabling “wireless electroceuticals”, logic-gated drug delivery, and dynamic mechanical training. Furthermore, this review highlights the emerging “Acoustic-Material-Biological” synergistic strategies, such as sonoporation-assisted gene transfection and mechano-electrical coupling, which provide controllable biointerfaces for influencing regenerative processes in complex tissues like bone, nerve, and tendon. Finally, we discuss critical challenges in acoustic dosimetry and envision an era driven by AI-optimized planning and wearable sono-therapy, highlighting future opportunities for precision regenerative medicine.