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.