Osteomyelitis, Copper, Bioactive glass, Antibacterial, Osteogenesis, Angiogenesis.
Irish Research Council (GOIPG/2015/3044). RCSI Office of Research and Innovation Seed Fund Award (Grant no. GR 14–0963) Science Foundation Ireland under Grant no. SFI/12/RC/2278 (the AMBER Centre) European Union for a Marie Curie European ReintegrationGrant under H2020 (Project Reference 659715). EU-FP7 Programme, Starting Independent Research Grant (Award No: 238685-CollRegen).
The bone infection osteomyelitis (typically by Staphylococcus aureus) usually requires a multistep procedure of surgical debridement, long-term systemic high-dose antibiotics, and - for larger defects - bone grafting. This, combined with the alarming rise in antibiotic resistance, necessitates development of alternative approaches. Herein, we describe a one-step treatment for osteomyelitis that combines local, controlled release of non-antibiotic antibacterials with a regenerative collagen-based scaffold. To maximise efficacy, we utilised bioactive glass, an established osteoconductive material with immense capacity for bone repair, as a delivery platform for copper ions (proven antibacterial, angiogenic, and osteogenic properties). Multifunctional collagen-copper-doped bioactive glass scaffolds (CuBG-CS) were fabricated with favourable microarchitectural and mechanical properties (up to 1.9-fold increase in compressive modulus over CS) within the ideal range for bone tissue engineering. Scaffolds demonstrated antibacterial activity against Staphylococcus aureus (up to 66% inhibition) whilst also enhancing osteogenesis (up to 3.6-fold increase in calcium deposition) and angiogenesis in vitro. Most significantly, when assessed in a chick embryo in vivo model, CuBG-CS not only demonstrated biocompatibility, but also a significant angiogenic and osteogenic response, consistent with in vitro studies. Collectively, these results indicate that the CuBG-CS developed here show potential as a one-step osteomyelitis treatment: reducing infection, whilst enhancing bone healing.
Ryan EJ, Ryan AJ, González-Vázquez A, Philippart A, Ciraldo FE, Hobbs C, Nicolosi V, Boccaccini AR, Kearney CJ, O'Brien FJ. Collagen scaffolds functionalised with copper-eluting bioactive glass reduce infection and enhance osteogenesis and angiogenesis both in vitro and in vivo. Biomaterials. 2019;197:405-416.
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