Ascorbate-loaded MgFe layered double hydroxide for osteomyelitis treatment

Bacterial infections evoke considerable apprehension in orthopedics. Traditional antibiotic treatments exhibit cytotoxic effects and foster bacterial resistance, thereby presenting an ongoing and formidable obstacle in the realm of therapeutic interventions. Achieving bacterial eradication and osteogenesis are critical requirements for bone infection treatment. Herein, we design and fabricate a nanoenzyme-mimicking drug through the co-precipitation process, integrating MgFe layered double hydroxide with ascorbic acid (AA@LDH), to facilitate the simultaneous presence of these two unique functionalities. Within a bacterial acidic milieu, the degradation of the AA@LDH nanosystem prompts ascorbic acid to undergo a pro-oxidative transformation, generating an abundance of reactive oxygen species (ROS). These ROS overwhelm bacterial cellular processes, including nucleic acid replication, cell wall construction, virulence factor production, biosynthetic pathways, and energy generation. This disruption culminates in substantial bacterial mortality, as substantiated by RNA sequencing data. Hence, the AA@LDH nano system exhibits an in vitro antibacterial rate of approximately 100 % and 99 %, against S.aureus and E. coli, respectivaly. Additionally, the AA@LDH could directly accelerate osteogenic differentiation in vitro, evidenced by a 50 % increase in alkaline phosphatase activity and a 270 % improvement in extracellular matrix mineralization capability. Moreover, it enhances osteointegration process in vivo by favorably reshaping the osteogenic immune microenvironment. This innovative nanosystem for delivery offers new strategies that concurrently combat bacterial infections, mitigate inflammation, and induce tissue regeneration, marking a significant advancement in the realm of advanced materials and its applications.