Biogenic Caralluma sinaica-derived silver nanoparticles as a synergistic antibacterial and osteoinductive...

Osteomyelitis is an inflammatory bone disease caused by infectious microorganisms. Challenges in treating chronic osteomyelitis include antibiotic resistance, inadequate immune response, and the need for surgical debridement. As an alternative treatment strategy, we developed a formulation of green phytosynthesized silver nanoparticles (AgNPs) and plant extract, as a novel multifunctional drug to achieve antibacterial and osteogenic activities in osteomyelitis.

Green silver nanoparticles (CS-AgNPs) were successfully phytosynthesized using Caralluma sinaica methanolic leaf extract. CS-AgNPs exhibited strong elemental purity as verified by EDX and XRD analyses. A Staphylococcus aureus-induced osteomyelitis mouse model was used as an in vivo model. Immune-histochemical analysis was used to study the effect of CS-AgNPs/PE on infected bone.

Functionally, CS-AgNPs, combined with plant extract (CS-AgNPs/PE), exhibited significant antibacterial potency. This hybrid formulation significantly reduced MIC and MBC values against Staphylococcus aureus and produced extensive membrane disruption, leakage of intracellular constituents, and higher ROS production. Additionally, CS-AgNPs/PE suppressed the development of biofilms, hemolysis production, and bacterial cell wall integrity. CS-AgNPs/PE reported no cellular toxicity in vitro and in vivo. Local treatment of IOM mice with CS-AgNPs/PE significantly inhibited bacterial burden and inflammatory response associated with reduced CD68-positive macrophage infiltration. Immune-histochemical analysis of treated infected bone area with CS-AgNPs/PE revealed significantly increased osteocalcin-positive osteoblasts, collagen deposition, osteoid thickness, and mineralized bone as compared to the non-treated group. A comparative study of different treatment groups in IOM mice attributed the osteoinductive effect of CS-AgNPs/PE to the phytochemicals of the PE.

Our data provide a novel green nanoparticles formulation with dual anti-bacterial and osteoinductive actions as a promising therapeutic strategy for chronic osteomyelitis.