Defect-Mediated Sonodynamic Catalysis on Calcium-Deficient Hydroxyapatite Nanoparticles Coordinating Bacterial Elimination and Bone Regeneration against Osteomyelitis.

Osteomyelitis, a skeletal infection, is commonly treated with long-term, high-dose antibiotics, carrying the risk of bacterial resistance and treatment failure. There is an urgent clinical need for effective non-antibiotic therapies. Sonodynamic therapy (SDT) activated by ultrasound (US) represents a promising alternative due to its deep tissue penetration and biosafety. Hydroxyapatite (HAP) is a naturally occurring mineral in the human body that exhibits excellent biocompatibility and osteogenic properties. However, the inherently low piezoelectric coefficient of pristine HAP restricts efficacy as a sonodynamic antibacterial agent. In this study, we developed a calcium-deficient HAP (DCP) with enhanced piezoelectric properties through crystal structure modulation via calcium vacancy engineering. This modification optimizes the band structure of DCP, significantly improving its sonodynamic performance under US irradiation. The modified material demonstrates strong bacterial membrane penetration and disruption capabilities, leading to antibacterial outcomes. Additionally, the facilitated electron transfer promotes charge accumulation, which further stimulates osteogenic regeneration and promotes bone formation and mitigates osteolytic damage. In vitro and in vivo results confirm that the DCP-based SDT system not only efficiently eradicates bacteria but also mitigates local inflammation, inhibits osteolytic damage, and supports bone repair. This metal-free, piezoelectric nanoplatform provides a controllable and clinically translatable strategy for treating osteomyelitis without conventional antibiotics.