Silicon incorporation into hydroxyapatite nanocarrier counteracts the side effects of vancomycin for efficient chronic osteomyelitis treatment

Local administration of antibiotics is a primary approach for treating chronic osteomyelitis (CO). However, clinically used antibiotic delivery systems exhibit suboptimal osteoinductivity, ascribed to the carrier material itself and the cytotoxicity of the loaded antibiotic, often leading to unsatisfactory treatment efficiency. To overcome this problem, we introduced Si into hydroxyapatite (HAp) nanocarriers by surface wrapping with a certain thickness of mesoporous bioactive glass (MBG). This facilitates controlled and sustained antibiotic release, while more importantly, silicon (Si) released from MBG counteracts the side effects of having a high antibiotic concentration at the defect site. Vancomycin-loaded HAp nanocarriers wrapped with MBG were shown to have a higher loading efficiency and more sustained antibiotic release behaviour. In vitro experiments using MC3T3-E1 cells showed that Si ions were effective in counteracting the negative effects of vancomycin on cell proliferation and osteogenic differentiation. In vivo implantation into a CO rat model showed that vancomycin-loaded MBG-wrapped HAp nanocarriers efficiently eliminated the infection and promoted superior bone healing at the fracture site compared to the control that did not release Si. This study highlights the important role of Si in neutralising the side effects of antibiotics, thus opening up a new design concept for biomaterials as antibiotic carriers for treating infection.