Abstract

Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilm formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortunately, enoxacin exerts both antibacterial and osteoclast inhibitory effects, playing a role in limiting infection and preventing bone loss. However, enoxacin lacks specificity in bone tissue and low bioavailability-related adverse effects, which hinders translational practice. Here, we developed a nanosystem (Eno@MSN-D) based on enoxacin (Eno)-loaded mesoporous silica nanoparticles (MSN), decorated with the eight repeating sequences of aspartate (D-Asp8), and coated with polyethylene glycol The release results suggested that Eno@MSN-D exhibits a high sensitivity to acidic environment. Moreover, this Eno@MSN-D delivery nanosystem exhibited both antibacterial and anti-osteoclast properties in vitro. The cytotoxicity assay revealed no cytotoxicity at the low concentration (20 μg/ml) and Eno@MSN-D inhibited RANKL-induced osteoclast differentiation. Importantly, Eno@MSN-D allowed the targeted release of enoxacin in infected bone tissue. Bone morphometric analysis and histopathology assays demonstrated that Eno@MSN-D has antibacterial and antiosteoclastic effects in vivo, thereby preventing implant-related infections and bone loss. Overall, our study highlights the significance of novel biomaterials that offer new alternatives to treat and prevent orthopaedic Staphylococcus aureus-related implantation infections and bone loss.

Highlights

  • Owing to the beneficial application of orthopaedic implants and improvement in treatments, patients affected by several orthopaedic diseases, including congenital malformations, acquired deformities, and osteoarthritis, as well as fractures can achieve satisfactory therapeutic effects

  • mesoporous silica nanoparticles (MSN) maintained a highly ordered mesoporous structure, which disappeared after enoxacin loading and polyethylene glycol (PEG)/D-Asp8 immobilisation, and the average particle size of enoxacin-loaded MSN (Eno@MSN)-D was larger than that of MSN and Eno@MSN, consistent with the results obtained in the dynamic light scattering (DLS) analysis (Figure 2D)

  • Conventional antibiotics limit the formation of bacterial biofilms, they ignore the fact that bacterial biofilms restrict the spread of antibiotics to the infected area, further lowering the concentration of antibiotics available to the infected area, as well as bone loss caused by osteoclast formation following orthopaedic implant-associated infections

Read more

Summary

Introduction

Owing to the beneficial application of orthopaedic implants and improvement in treatments, patients affected by several orthopaedic diseases, including congenital malformations, acquired deformities, and osteoarthritis, as well as fractures can achieve satisfactory therapeutic effects. The incidence of infection in orthopaedic surgery is approximately 5%, with post-operative infection rates of closed fractures making up 3.6–8.1%. The lack of blood supply around the implant and the formation of bacterial biofilm (Lazzarini et al, 2004; Li et al, 2019), usually result in ineffective anti-infection treatments. This increases the duration of hospital stays and the total cost and reduces the effectiveness of rehabilitation

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call