A research team from the National University of Singapore has published a breakthrough study in Advanced Science, revealing that physical squeezing can direct mesenchymal stem cells (MSCs) to differentiate into bone-forming osteoblasts. This discovery provides a new, chemistry-free method for bone tissue regeneration and is expected to advance the field of regenerative medicine.

The team designed a microchannel system that mimics the physical environment of tissue interstices in the body. When MSCs are forced through narrow channels only 3 micrometers wide, their nuclei undergo significant deformation, activating the key osteogenic transcription factor RUNX2, with expression levels increasing by more than 40%. Remarkably, this osteogenic tendency persists even after the cells exit the channels, indicating a "mechanical memory" effect.

"Traditional approaches rely on chemical signals or genetic editing to guide stem cell differentiation, but our study shows that pure physical confinement can effectively control cell fate," said Assistant Professor Andrew Holle, the lead researcher. The technique requires no exogenous growth factors or genetic modification; simply passing cells through the microchannels yields large numbers of pre-differentiated osteoblast precursors, offering a low-cost and highly safe advantage.

The team plans to further explore the technology's applications in fracture repair and cancer therapy. Preliminary hypotheses suggest that mechanically preconditioned MSCs may gain enhanced ability to penetrate tumor tissue, improving the delivery efficiency of cell-based therapies. Additionally, the discovery could be extended to induced pluripotent stem cells (iPSCs), opening new possibilities for broader regenerative medicine applications.