Effective tissue regeneration requires precise spatiotemporal therapeutic delivery while maintaining scaffold mechanical integrity, which remains a major challenge in regenerative medicine. Here, we present an ultrasound (US)-activated tissue regeneration platform based on engineered osteogenic microbubbles (MMB-BMPs) embedded in a dynamic hyaluronic acid hydrogel (dHA), forming a mechanically robust scaffold (dHAMBH). Upon repeated US stimulation at the resonant frequency, MMB-BMPs underwent stable oscillation within the hydrogel, enabling stepwise, on-demand release of iron oxide nanoparticles (IONPs) and bone morphogenetic protein-2 (BMP-2), while maintaining scaffold integrity after multiple stimulations cycles. This controlled co-delivery enhances osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hMSCs). In a mouse critical-sized calvarial defect model, the dHAMBH hydrogel combined with US stimulation accelerated bone regeneration, achieving a 1.7-fold increase in new bone volume compared with the non-US stimulated control. Overall, this work establishes a US-activated platform that enables precise, repeatable therapeutic delivery to enhance tissue regeneration.

Silica nanoparticles have been studied extensively in biomedical field due to their high biocompatibility, controllable morphology and so on. They can be used both as the drug carrier and imaging vehicle. Here, an aminated ultra-small silica nanoparticle based system is developed with various functionalities. Multiple molecules including fluorophore, folic acid, and antibody are coupled to this system to achieve specific applications such as bacterial/cell labelling and recognition.