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

Abstract

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 Ti 3 C 2 nanosheets (HN-Ti 3 C 2 ) for highly efficient sonodynamic therapy of osteomyelitis and bone regeneration. Results: Ti 3 C 2 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-Ti 3 C 2 shows excellent 99.75% antibacterial effectiveness against MRSA. In addition, HN-Ti 3 C 2 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-Ti 3 C 2 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-Ti 3 C 2 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-Ti 3 C 2 successfully eliminated the infection and significantly improved bone regeneration under US irradiation. Conclusion: This study indicates that engineered HN-Ti 3 C 2 is a distinctive nanocomposite for successful osteomyelitis treatment.

A Distinctive Insight into Inorganic Sonosensitizers: Design Principles and Application Domains

“…Furthermore, MOF and its derivatives as the popular family of sonosensitizers were underscored to repress bacteria and resist inflammation, e.g., porphyrin‐based MOF coupled on Ti 3 C 2 nanosheets with a Schottky junction. [ 199 ] A typical instance was cerium‐based MOF (CeTCPP) decorated with Au nanoparticles, [ 200 ] and under ultrasound irradiation, the CeTCPP‐Au showed superior antibacterial efficacy of over 99% against Staphylococcus aureus and Escherichia coli with good biocompatibility, promising the highly‐effective therapy of osteomyelitis. Additionally, other emerging inorganic sonosensitizers also showed excellent anti‐bacteria and anti‐infection performances including Au@Cu 2 O hybrid nanocubes, [ 201 ] oxygen vacancies‐rich Sodium molybdenum bronze nanoparticles (SMB NPs).…”

Research Progress on Ti3C2Tx-Based Composite Materials in Antibacterial Field

“…This visible light-responsive organic–inorganic hybrid achieves antibacterial efficiencies of 99.86% and 99.92% against S. aureus and E. coli , respectively, within 10 min. Porphyrin MOFs combined with Ti 3 C 2 T x not only kill drug-resistant bacteria by generating abundant ROS but also promote the proliferation of stem cells by regulating the cell cycle, DNA replication, and apoptosis [ 112 ]. They promote osteogenic differentiation through key signaling pathways, including calcium, Wnt, and TGF-beta signaling pathways.…”

Sonodynamic therapy-based nanoplatforms for combating bacterial infections

“…Due to the immunoregulation and osteogenesis promotion playing a pivotal role in osteomyelitis treatment, novel antimicrobial nanomaterials for inducing bone regeneration have been designed for adjuvant SDT of osteomyelitis. Recently, Wang et al synthesized a porphyrin-based-MOF modified Ti 3 C 2 hybrid nanomaterials (HNTM/Ti 3 C 2 ) for enhancing the SDT effect [117] . Based results of the protein and gene expression in human bone marrow mesenchymal stem cells (hBMSCs), it was demonstrated that the HNTM/Ti 3 C 2 significantly upregulation the osteogenesis-related protein expression levels of alkaline phosphatase (ALP) and osteopontin and enhanced the runt-related transcription factor 2 (RUNX2), osteopontin, ALP, BMP2, COL-1, and osteocalcin genes expression level.…”