Abstract
Ultrasound-responsive hydrogels have garnered significant attention for the treatment of bone and cartilage defects owing to their non-invasive regulation, precise drug delivery, and capacity to promote tissue regeneration. This review provides a comprehensive overview of the current research landscape on ultrasound-responsive hydrogels, encompassing their preparation strategies, distinctive advantages, application domains, and therapeutic mechanisms. Preparation methods predominantly involve physical and chemical cross-linking techniques, while the response mechanisms are mediated by both thermal and non-thermal effects of ultrasound. Ultrasound endows hydrogels with unique characteristics, including non-invasiveness, spatiotemporal controllability, the facilitation of cell migration, and the potential for synergistic therapy. The integration of ultrasound-responsive hydrogels with emerging technologies-such as nanotechnology and genetic engineering-has expanded their applicability in the regeneration of bone and cartilage defects, as well as in the treatment of associated infections and tumors. The underlying biological mechanisms are diverse, involving key signalling pathways such as MAPK/ERK, BMP/Smad, and HIF-1α/VEGF. In summary, ultrasound-responsive hydrogels demonstrate considerable promise and distinct advantages in bone and cartilage tissue engineering. Nevertheless, several challenges remain, including the development of more versatile preparation strategies, more precise control over ultrasound parameters, and a deeper understanding of their mechanisms of action-all of which merit further investigation.