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.