The overarching research aim of this proposal is to address the clinical problem of osteomyelitis, i.e. bone infection, by developing a biomaterial scaffold that eliminates bacteria while regenerating bone simultaneously. For that, the biomaterial scaffold combines, for the first time, the controlled delivery of osteoanabolic genetic cargo for bone healing with non-antibiotic antimicrobial nanoparticles (a-NPs). During the project, I assessed the effect of various metal ions, such as zinc and copper, on the toxicity of most common models of bacteria, gram-positive Staphylococcus aureus (S.aureus) and gram-negative Escherichia coli (E.coli) and viability of human mesenchymal stem cells (hMSCs) in 2D cultures showing that the dosages higher than 5 mM result in bacterial lysis. These antimicrobial ions were then incorporated into inorganic materials: nanohydroxyapatite (a-nHA) and bioglass (a-BG). I showed that the incorporation of Cu-BG into collagen scaffolds significantly reduces the attachment of S.aureus equipping the biomaterial scaffold with antimicrobial properties. During the project, I evaluated various genetic cargoes showing that antagomiR-138 exhibits favourable osteogenic properties stimulating human mesenchymal stem cells to differentiate into bone cells. I have also assessed the osteogenic potential of miR-26a and antagomiR-133a in vitro. The genetic cargoes were further incorporated into collagen scaffolds and assessed in vivo. The antagomiR-138 was incorporated into antimicrobial scaffolds, which contained Cu-BG. Its osteogenic and angiogenic potential was confirmed using the ex ovo embryo chick model. Based on the results, the scaffolds combining antimicrobial nanoparticles with osteogenic genetic cargoes might be a potential solution for treating infected bone tissue.
