Ultrasound-controlled MXene-based Schottky heterojunction improves anti-infection and osteogenesis properties

Background: The current clinical treatment of osteomyelitis is limited by the emergence of drug-resistant bacteria, which often leads to the failure of traditional antibiotic treatment and large bone defects. Sonodynamic therapy (SDT) is a new strategy that is widely used to overcome the problem of bacterial resistance to antibiotic therapy as well as poor tissue penetration using near-infrared light in photodynamic therapy (PDT). Therefore, it is necessary to develop a new sonosensitizer that can kill bacteria and promote bone repair. Methods: Herein, we developed a sonosensitizer, porphyrin metal-organic framework (HNTM), with a Schottky junction modified by Ti₃C₂ nanosheets (HN-Ti₃C₂) for highly efficient sonodynamic therapy of osteomyelitis and bone regeneration. Results: Ti₃C₂ greatly improves the acoustic catalytic performance by rapidly transferring the charge carriers generated by HNTM under ultrasound (US) irradiation, which killing drug-resistant bacteria through the generation of large amounts of reactive oxygen species (ROS). And HN-Ti₃C₂ shows excellent 99.75% antibacterial effectiveness against MRSA. In addition, HN-Ti₃C₂ generates a sonocurrent under low-intensity US to promote the repair of bone defects for a long time period. Mechanistic research using CCK-8 and RNA-seq showed that HN-Ti₃C₂ nanocomposites can promote the proliferation of stem cells by regulating the cell cycle, DNA replication, and apoptosis. In addition, after low-intensity US irradiation, HN-Ti₃C₂ promotes osteogenic differentiation via some key signaling pathways, including the calcium, Wnt, and TGF-beta signaling pathways, according to the Kyoto Encyclopedia of Genes and Genomes (KEGG). In a MRSA-infected rat tibial osteomyelitis model, HN-Ti₃C₂ successfully eliminated the infection and significantly improved bone regeneration under US irradiation. Conclusion: This study indicates that engineered HN-Ti₃C₂ is a distinctive nanocomposite for successful osteomyelitis treatment.