Journal
BIOMATERIALS
Volume 197, Issue -, Pages 405-416Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.01.031
Keywords
Osteomyelitis; Copper; Bioactive glass; Antibacterial; Osteogenesis; Angiogenesis
Funding
- Irish Research Council [GOIPG/2015/3044]
- RCSI's Office of Research and Innovation Seed Fund Award [GR 14-0963]
- Science Foundation Ireland [SFI/12/RC/2278]
- European Union [659715]
- EU-FP7 Programme, Starting Independent Research Grant [238685-CollRegen]
- SFI AMBER
- SFI PIYRA
- ERC StG 2D Nanocaps
- ERC CoG 3D2DPrint
- Horizon2020 NMP Co-Pilot
- Marie Curie Actions (MSCA) [659715] Funding Source: Marie Curie Actions (MSCA)
- Irish Research Council (IRC) [GOIPG/2015/3044] Funding Source: Irish Research Council (IRC)
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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 bio-compatibility, 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.
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