A new treatment for Osteomyelitis?
A potential new treatment for Osteomyelitis: Incorporating copper-eluting bioactive glass with collagen scaffolds.
In a recent paper available here, RCSI’s Tissue Engineering Research Group (TERG), led by Prof. Fergal O’Brien, explores a novel approach to the management of osteomyelitis, with the potential for other illness management applications.
This condition is associated with significant patient morbidity and cost to health systems, often requiring surgical debridement of necrotic bone, followed by prolonged administration of intravenous antibiotics. Successful treatment is hampered by poor blood flow to the necrotic area and the continued emergence of antibiotic-resistant bacteria, particularly in the nosocomial setting. The stimulation of bone regeneration to fill defects left in the bone holds equal importance in regards to treatment.
The authors hypothesise that combining copper-doped bioactive glass with a porous 3D collagen scaffold that has proven regenerative capacity would result in an off-the-shelf scaffold for osteomyelitis treatment that elicits osteogenesis and angiogenesis, whilst crucially limiting infection.
They determined a concentration of copper chloride capable of killing S. Aureus, while at the same time minimizing damage to mammalian cells such as osteoblasts. The copper ions were then incorporated into a bioactive glass used as a local delivery vehicle within a collagen scaffold.
The viability of S. Aureus was clearly shown to be reduced by these copper-doped bioactive glass collagen scaffolds (CuBG-CS). Osteo- and angiogenesis in-vitro was similarly enhanced by these scaffolds, as was a chick embryo ex-ovo model, proving their biocompatibility.
These results indicate that the CuBG-CS developed here show potential to be used in the osteomyelitis defect site by simultaneously limiting infection whilst promoting bone healing. This appears to be the first study to demonstrate successful incorporation of copper-doped bioactive glass into a natural polymer-based scaffold.
Copper ions have demonstrated previously that they have a pro-angiogenic effect on endothelial cells in vitro by upregulating VEGF production and enhancing proliferation. Research has also found that the combination of copper sulphate with the growth factors VEGF or FGF-2 on endothelial cells significantly enhanced the complexity of the angiogenic networks with a synergistic effect.
While the chick embryo model offers several economic and practical advantages over other models and it provided valuable insight into the in-vivo osteogenic and angiogenic effect of the scaffolds, a limitation to highlight is that the chick embryo model does not encompass an infection aspect, essential in assessing the suitability of potential new treatment strategies for osteomyelitis.
In this study, the authors used the chick embryo as a preliminary model to predict the response of the scaffolds within a complex biological environment, before assessing the scaffolds in a full-scale osteomyelitis animal model.
Ultimately, osteomyelitis is a notoriously difficult-to-treat infection that typically requires a two-stage treatment. Our researchers successfully produced a single-step approach to osteomyelitis treatment, consisting of collagen copper-doped bioactive glass scaffolds that stimulate osteogenesis and angiogenesis both in vitro and in vivo, while also being capable of antibacterial activity without the use of antibiotics.
Under the application of this novel off-the-shelf treatment, the need for bone grafting and antibiotics might be reduced, which would consequentially relieve strain on health systems by reducing the length of patients’ hospital stays and the costs associated with that.
In the future, there is also capacity for the platform system to be further modified and used to deliver a variety of other non-antibiotic antimicrobial metal ion-doped minerals to address alternative health concerns.
Journal Article Information:
Collagen scaffolds functionalised with copper-eluting bioactive glass reduce infection and enhance osteogenesis and angiogenesis both in vitro and in vivo
Biomaterials. 2019 Mar;197:405–416.
DOI: https://doi.org/10.1016/j.biomaterials.2019.01.031
