Targeting immuno-microenvironment regulation for treating infected bone defects

Infectious bone defect is a challenging clinical problem. Existing treatments struggle to achieve bacterial clearance while simultaneously suppressing the inflammatory microenvironment. Immune regulation is an important approach to addressing the dual challenge of antibacterial and anti-inflammatory, but the specific regulatory methods and related mechanisms have not been elucidated. Here, by screening different bacterial outer membrane vesicles (OMVs), we found that the outer membrane vesicles of Nissle1917 (EcN) (EOMV) possess dual properties of self-antibacterial activity and immune activation. Additionally, using PLLA porous scaffolds loaded with gene-edited macrophages (Hsp-m) can control IL-10 release through in situ sonothermal effects, thereby regulating the inflammatory microenvironment. In this study, we co-cultured the engineered scaffolds with mBMSCs and found that after ultrasound treatment, it promoted the osteogenic gene expression of mBMSCs