One step solution for fighting bacteria and growing bone

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Science Translational Medicine  13 Feb 2019:
Vol. 11, Issue 479, eaaw5326
DOI: 10.1126/scitranslmed.aaw5326


The delivery of copper ions from collagen-bioactive glass composite scaffolds offers a promising one-step approach to treating bone infections while also promoting new bone and blood vessel formation.

The incidence of bone infections, also known as osteomyelitis, is increasing as more surgeries for joint replacement and fracture repair are being performed. Treatment can range from systemic antibiotic delivery to multistep treatment, including surgery to remove the necrotic bone, implantation of an autologous bone graft to fill the defect, and additional antibiotic delivery. Despite advances in treatment, bone infections remain very difficult to treat, with failure rates as high as 30%. The growing frequency of patients with antibiotic resistance creates additional challenges in treating infections. As an alternative to antibiotics, copper is a well-known antimicrobial that is also capable of enhancing bone growth by inducing osteogenesis, as well as increasing vascularization by promoting vascular endothelial growth factor (VEGF) production. With this in mind, the authors proposed the delivery of copper-doped bioactive glass using a collagen scaffold to create a multifunctional material for fighting infection and supporting tissue regeneration, osteogenesis, and angiogenesis.

Collagen-bioactive glass (CBG) composite scaffolds were fabricated with a range of concentrations from 0 to 300% bioactive glass (with and without copper doping) to collagen. The scaffolds were manufactured through a freeze-drying process that results in highly porous scaffolds, where porosity is important for cell migration and nutrient diffusion. In vitro analysis, using Staphylococcus aureus, demonstrated copper-doped CBG scaffolds inhibited bacterial growth with increased inhibition up to 66% at higher copper concentrations. Copper eluting scaffolds were also capable of maintaining mammalian cell viability, improving calcium deposition, and increasing VEGF production compared with collagen-only controls. Similar osteogenic and angiogenic trends were observed in vivo using a chick embryo model. Interestingly, both in vitro and in vivo results indicate a moderate concentration of copper is ideal for enhancing angiogenesis. Due to these results, the authors suggest tailoring the treatment depending on the relative need to fight infection (recommend high copper dose) versus augment tissue regeneration (recommend moderate copper dose).

The delivery of copper ions from CBG composite scaffolds offers a promising one-step approach to the treatment of osteomyelitis as well as promotes new bone and blood vessel formation. Nonetheless, ongoing research is needed to evaluate the proposed materials in larger osteomyelitis animal models.

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