Abstract
Chronic infectious bone destruction diseases, such as periodontitis, pose a significant global health challenge. Repairing the bone loss caused by these chronic infections remains challenging. In addition to pathogen removal, regulating host immunity is imperative. The retention of neutrophil extracellular traps (NETs) in chronic infectious niches is found to be a barrier to inflammation resolution. However, whether ruining the existing NETs within the local infectious bone lesions can contribute to inflammation resolve and bone repair remains understudied. Herein, a nanocapsuled delivery system that scavenges NETs dual-responsively to near-infrared light as a switch and to NETs themselves as a microenvironment sensor is designed. Besides, the photothermal and photodynamic effects endow the nanocapsules with antibacterial properties. Together with the ability to clear NETs, these features facilitate the restoration of the normal host response. The immunocorrective properties and inherent pro-osteogenic effects finally promote local bone repair. Together, the NET scavenging nanocapsules address the challenge of impaired bone repair in chronic infections due to biased host response caused by excessive NETs. This study provides new concepts and strategies for repairing bone destruction attributable to chronic infections via correcting biased host responses in chronic infectious diseases.