Small extracellular vesicles with nanomorphology memory promote osteogenesis

Area of Science:

• Biomaterials Science
• Cell Biology
• Regenerative Medicine

Background:

• Nanotopography guides cell behavior, influencing cellular mechanical memory.
• Small extracellular vesicles (sEVs) are crucial mediators of intercellular communication.
• Harnessing sEVs for tissue regeneration requires understanding their environmental interactions.

Purpose of the Study:

• To introduce and investigate the concept of

Main Methods:

• Nanotopography (Ti8) was created on titanium plates to culture human mesenchymal stem cells (hMSCs).
• sEVs were extracted from hMSCs cultured on Ti8 for 21 days (Ti8-21-sEV).
• Ti8-21-sEVs were characterized and applied to 3D printed scaffolds for *in vitro* and *in vivo* bone regeneration studies.

Main Results:

• Ti8-21-sEVs demonstrated enhanced pro-osteogenesis capacity *in vitro* and *in vivo*.
• RNA sequencing revealed Ti8-21-sEVs activate key osteogenic pathways (PI3K-AKT, MAPK, focal adhesion, ECM-receptor interaction).
• Scaffolds decorated with Ti8-21-sEVs showed superior bone ingrowth in a rabbit femoral condyle defect model.

Conclusions:

• sEVs can acquire and retain