Vancomycin-loaded bone substitute as a ready-to-use drug delivery system to treat osteomyelitis

Microbial infections of bones, particularly after joint replacement surgery, are a common occurrence in clinical settings and often lead to osteomyelitis (OM). Unfortunately, current treatment approaches for OM are not satisfactory. To address this issue, this study focuses on the development and evaluation of an injectable magnesium oxide (MgO) nanoparticle-coordinated phosphocreatine-grafted chitosan hydrogel (CMPMg-VCM) loaded with varying amounts of vancomycin (VCM) for the treatment of OM. The results demonstrate that the loading of VCM does not affect the formation of the injectable hydrogel, and the MgO-incorporated hydrogel exhibits anti-swelling properties. The release of VCM from the hydrogel effectively kills staphylococcus aureus bacteria, with CMPMg-VCM (50) showing the highest antibacterial activity even after prolonged immersion in PBS solution for 12 days. Importantly, all the hydrogels are non-toxic to MC3T3-E1 cells and promote osteogenic differentiation through the early secretion of alkaline phosphatase and calcium nodule formation. Furthermore, in vivo experiments using a rat OM model reveal that the CMPMg-VCM hydrogel effectively kills and inhibits bacterial growth, while also protecting the infected bone from osteolysis. These beneficial properties are attributed to the burst release of VCM, which disrupts bacterial biofilm, as well as the release of Mg ions and hydroxyl by the degradation of MgO nanoparticles, which inhibits bacterial growth and prevents osteolysis. Overall, the CMPMg-VCM hydrogel exhibits promising potential for the treatment of microbial bone infections.

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Vancomycin-Loaded in situ Gelled Hydrogel as an Antibacterial System for Enhancing Repair of Infected Bone Defects

Sun,

Wang,

Zhang

et al. 2024

IJN

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Purpose During treatment of infected bone defects, control of infection is necessary for effective bone repair, and hence controlled topical application of antibiotics is required in clinical practice. In this study, a biodegradable drug delivery system with in situ gelation at the site of infection was prepared by integrating vancomycin into a polyethylene glycol/oxidized dextran (PEG/ODEX) hydrogel matrix. Methods In this work, PEG/ODEX hydrogels were prepared by Schiff base reaction, and vancomycin was loaded into them to construct a drug delivery system with controllable release and degradability. We first examined the microstructure, degradation time and drug release of the hydrogels. Then we verified the biocompatibility and in vitro ability of the release system. Finally, we used a rat infected bone defect model for further experiments. Results The results showed that this antibacterial system could be completely biodegradable in vivo for 56 days, and its degradation products did not cause specific inflammatory response. The cumulative release of vancomycin from the antibacterial system was 58.3% ± 3.8% at 14 days and 78.4% ± 3.2% at 35 days. The concentration of vancomycin in the surrounding environment was about 1.2 mg/mL, which can effectively remove bacteria. Further studies in vivo showed that the antibacterial system cleared the infection and accelerated repair of infected bone defects in the femur of rats. There was no infection in rats after 8 weeks of treatment. The 3D image analysis of the experimental group showed that the bone volume fraction (BV/TV) was 1.39-fold higher ( p < 0.001), the trabecular number (Tb.N) was 1.31-fold higher ( p < 0.05), and the trabecular separation (Tb.Sp) was 0.58-fold higher than those of the control group ( p < 0.01). Conclusion In summary, this study clearly demonstrates that a clinical strategy based on biological materials can provide an innovative and effective approach to treatment of infected bone defects.

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Vancomycin-loaded bone substitute as a ready-to-use drug delivery system to treat osteomyelitis

Cited by 3 publications

References 41 publications

Recent advances in nanostructured delivery systems for vancomycin

Recent advances in nanostructured delivery systems for vancomycin

An injectable magnesium-coordinated phosphate chitosan-based hydrogel loaded with vancomycin for antibacterial and osteogenesis in the treatment of osteomyelitis

Vancomycin-Loaded in situ Gelled Hydrogel as an Antibacterial System for Enhancing Repair of Infected Bone Defects

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