Dual-synergistic engineered MXene sonosensitizer with stabilized semiquinone radicals enables biofilm eradication and immunomodulatory bone regeneration in osteomyelitis

Deep colonization of drug-resistant biofilms and impaired bone regeneration within the infectious microenvironment represent two major bottlenecks in the clinical management of osteomyelitis. Herein, we design a dually synergistically modified Ti 3 C 2 MXene sonosensitizer. Lattice strain is introduced via Zn 2+ substitution doping, while interfacial passivation is achieved by coordination-stabilized dopamine semiquinone radicals. Such engineering extends the carrier lifetime by 86-fold, enabling efficient generation of hydroxyl radicals under ultrasound irradiation. This engineered material exhibits triple biofunctional activities: it eliminates over 99.9% of MRSA biofilms in vitro and downregulates bacterial drug-resistance pathways; sustained Zn 2+ release polarizes macrophages toward the pro-repair M2 phenotype to remodel the inflammatory microenvironment of infected tissues; in a rat osteomyelitis model, a single local administration combined with ultrasound eradicates deep-seated infection, facilitates collagen deposition and bone regeneration, with favorable biosafety both in vitro and in vivo . This work offers a strategy based on novel multifunctional bioactive materials for treating infectious bone defects, holding promising potential for clinical translation.