A microenvironment responsive nanoparticle regulating osteoclast fate to promote bone repair in osteomyelitis

Osteomyelitis exhibits bone defects in an inflammatory and acid microenvironment. As a crucial factor in this inflammation responses, the macrophage-osteoclast axis is absolutely the core to regulate. The research explored a shell-core structured biomaterial, consisting of a gelatin nanoparticle (GNP) platform loaded with bone morphogenetic protein 9 (BMP9) and coated with a metal phenolic network (TA-Ce), which exhibited adaptive sensitivity to pH values. Extracellularly, it rapidly responded to lower pH, achieving specific release in an inflammatory microenvironment. Intracellularly, it impacted the formation, function, and differentiation of osteoclasts through the macrophage-osteoclast axis, thereby promoting bone defect repair. <i>In vivo</i> and <i>in vitro</i> studies showed GNPs-BMP9@TA-Ce regulated osteoclasts to optimize osteomyelitis treatment strategies, highlighting the potential of modified nanobiomaterials for clinical application.