Bacterial Capture‐Killing Capsules with Remodeling Bone Immune Microenvironment for the Effective Treatment of Osteomyelitis

Abstract Osteomyelitis represents a significant health concern, characterized by a bacterial infection that can potentially present a considerable challenge to clinical treatment. Current treatment strategies, including prolonged antibiotic regimens and surgical debridement, often fail to adequately resolve infection or support bone regeneration, largely due to the pathogen‐induced dysregulation of the bone microenvironment. This study reports a multifunctional capsule that achieves coordinated bacterial capture‐killing and immunomodulatory within osseous tissue, effectively resolving the dual pathological challenges of persistent infection microenvironment and dysregulated bone regeneration inherent to osteomyelitis. The capsules, PC‐O@TOB, are based on the Schiff base reaction of procyanidins (PC) with the amino of Lysine6‐osteogenic growth peptide (K6‐OGP) and tobramycin (TOB), which allows for efficient loading and controllable release of K6‐OGP and TOB. In vitro and in vivo studies demonstrated that PC‐O@TOB exhibits dual functionality: potent bactericidal activity through bacterial capture and localized antibiotic delivery, and microenvironmental remodeling via ROS scavenging and M2 macrophage polarization. This immunomodulatory effect synergizes with the capsule's osteogenic and angiogenic properties to accelerate bone repair. The strategy based on antibacterial and later bone microenvironment remodeling has opened up a new way for the treatment of osteomyelitis.