Abstract: Ultrasound (US) has evolved from a predominantly diagnostic modality into a versatile therapeutic stimulus capable of controlling biological and material responses with considerable spatial and temporal precision. Ultrasound-activated biomaterials integrate acoustic energy with responsive carriers, hydrogels, nanoparticles, microbubbles, nanodroplets, and electroactive scaffolds to enable externally controlled drug release, gene delivery, barrier modulation, and tissue regeneration. The principal mechanisms include stable and inertial cavitation, acoustic streaming, radiation force, localized heating, sonoporation, mechanotransduction, and sonochemical generation of reactive oxygen species. These mechanisms can be exploited independently or in combination to generate pulsatile, delayed, sustained, or on-demand release profiles. Microbubbles and phase-change nanodroplets are particularly attractive because they efficiently convert acoustic energy into mechanical effects, whereas liposomes, polymeric nanoparticles, micelles, and hydrogels provide versatile platforms for transporting small molecules, nucleic acids, proteins, and cells. In regenerative medicine, low-intensity pulsed ultrasound and ultrasound-responsive scaffolds can modulate osteogenesis, angiogenesis, wound healing, stem-cell differentiation, and neural repair. However, acoustic heterogeneity, material polydispersity, bioeffects, immunogenicity, manufacturing reproducibility, and regulatory classification remain important barriers to clinical translation. This mini-review summarizes the physical mechanisms underlying ultrasound activation, discusses major classes of responsive biomaterials, examines applications in spatiotemporal drug delivery and regenerative medicine, and outlines design, safety, and translational considerations. Future progress will depend on standardized acoustic dosimetry, multimodal imaging, adaptive ultrasound control, scalable manufacturing, and biomaterials capable of integrating therapeutic delivery with tissue-specific biological signaling.
Keywords: ultrasound-responsive biomaterials, spatiotemporal drug delivery, hydrogels, piezoelectric scaffolds, regenerative medicine, mechanotransduction