NIR-II Responsive Multifunctional Scaffold Enabling “Kill-Modulation-Build” Synergistic Therapy for Infectious Bone Defects

Infectious bone defects present dual challenges: eliminating bacteria and regenerating tissue, which are further complicated by biofilm formation, antibiotic resistance, and chronic inflammation. Here, a near-infrared-II (NIR-II) responsive fibrous scaffold (AIE NPs@BP NSs@FSs) that employs a sequential “Kill–Modulation–Build” therapeutic strategy—referring to infection clearance, immune regulation, and bone repair is developed. Upon NIR-II irradiation, aggregation-induced emission nanoparticles (AIE NPs) produce localized hyperthermia, which eliminates bacteria and biofilms, offering a non-antibiotic solution that reduces the risk of resistance development. Moreover, black phosphorus nanosheets (BP NSs) scavenge reactive oxygen species (ROS) and reprogram macrophages toward a pro-regenerative M2 phenotype. This immunomodulatory shift enhances endothelial migration, neovascularization, and osteogenic differentiation of bone marrow stem cells. With excellent biocompatibility and biomimetic architecture, the scaffold supports coordinated antibacterial, immunoregulatory, and osteoinductive responses. This work provides a promising platform for treating complex infected bone defects by combining photothermal therapy with immune and regenerative modulation.