Antibacterial Peptides-Produced Cell Hydrogel Eliminates Intracellular Pathogens and Remodels Immune Microenvironment for Osteomyelitis Therapy

Featuring bacterial invasion and colonization within cells, chronic infection-induced immune suppression, and inflammatory cell infiltration, osteomyelitis is currently an intractable and recurrent bone disease. In this study, an injectable hydrogel that gels in situ and is loaded with engineered antimicrobial cells (LL37-MSC@OCAHM) is developed. This anti-inflammatory hydrogel not only maintains cell activity in the inflammatory environment but also releases magnesium ions (Mg 2+ ) to promote the differentiation of MSCs into bone-forming cells, contributing to bone mass formation, enhancing bone repair, and accelerating bone healing. The engineered cells continuously produce antimicrobial peptides of LL37, which effectively kill both extracellular and intracellular bacteria at the osteomyelitis site. Additionally, cell hydrogel also modulates the immune response by shifting the osteomyelitis environment from pro-inflammatory to anti-inflammatory, reducing the infiltration of immune cells and myeloid-derived suppressor cells (MDSCs). We also demonstrated its ability to activate immune responses and generate immune memory, thereby preventing the recurrence of secondary infections. This study introduces an engineered cell-based approach that combines active antimicrobial effect, immune modulation, and bone repair, for effectively eliminating osteomyelitis infections and preventing recurrence.