@article{Ren2026, 
author = {Lili Ren and Jingyi Su and Yuxuan Chen and Zhixuan Wang and Li Min Tay and Wenjing Yang and Lixing Weng and Siyu Wang and Chenjie Xu and Lianhui Wang and Yu Gao},
title = {Dynamic hydrogels with repeatable ultrasound-activated microbubble oscillation enable stepwise spatiotemporal growth factor release for tissue regeneration},
year = {2026},
journal = {Nano Research},
keywords = {ultrasound stimulation, controlled drug delivery, microbubbles, stable oscillation, tissue regeneration},
url = {https://www.sciopen.com/article/10.26599/NR.2026.94909107},
doi = {10.26599/NR.2026.94909107},
abstract = {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.}
}