In vivo circRNA-engineered macrophages mediate localized MMP9 neutralization to rejuvenate aged bone - PubMed
4 hours ago
- #Bone Rejuvenation
- #Macrophages
- #circRNA
- Aging leads to osteoporosis, delayed fracture repair, and osteoarthritis, with MMP9 identified as a key factor through transcriptomic analysis of older patients.
- An in vivo circRNA-based antibody-engineering strategy targets macrophages to produce anti-MMP9 antibodies, using apoptosis-mimicking lipid nanoparticles (aMMP9-LNP) for enhanced specificity.
- In aged mice, systemic aMMP9-LNP reduced stem cell senescence, boosted osteogenesis, accelerated fracture repair, and mitigated cartilage degeneration by blocking MMP9 and restoring cellular balance.
- The approach enables systemic, targeted MMP9 neutralization via inflammation-guided chemotaxis, with biodistribution confirming bone-targeted delivery and preserved tissue homeostasis for translational potential.