Abstract
BackgroundBioactive glasses are traditionally associated with bonding to bone through a hydroxycarbonate apatite (HCA) surface layer but the release of active ions is more important for bone regeneration. They are now being used to deliver ions for soft tissue applications, particularly wound healing. Cobalt is known to simulate hypoxia and provoke angiogenesis. The aim here was to develop new bioactive glass compositions designed to be scaffold materials to locally deliver pro-angiogenic cobalt ions, at a controlled rate, without forming an HCA layer, for wound healing applications.MethodsNew melt-derived bioactive glass compositions were designed that had the same network connectivity (mean number of bridging covalent bonds between silica tetrahedra), and therefore similar biodegradation rate, as the original 45S5 Bioglass. The amount of magnesium and cobalt in the glass was varied, with the aim of reducing or removing calcium and phosphate from the compositions. Electrospun poly(ε-caprolactone)/bioactive glass composites were also produced. Glasses were tested for ion release in dissolution studies and their influence on Hypoxia-Inducible Factor 1-alpha (HIF-1α) and expression of Vascular Endothelial Growth Factor (VEGF) from fibroblast cells was investigated.ResultsDissolution tests showed the silica rich layer differed depending on the amount of MgO in the glass, which influenced the delivery of cobalt. The electrospun composites delivered a more sustained ion release relative to glass particles alone. Exposing fibroblasts to conditioned media from these composites did not cause a detrimental effect on metabolic activity but glasses containing cobalt did stabilise HIF-1α and provoked a significantly higher expression of VEGF (not seen in Co-free controls).ConclusionsThe composite fibres containing new bioactive glass compositions delivered cobalt ions at a sustained rate, which could be mediated by the magnesium content of the glass. The dissolution products stabilised HIF-1α and provoked a significantly higher expression of VEGF, suggesting the composites activated the HIF pathway to stimulate angiogenesis.
Highlights
Bioactive glasses are traditionally associated with bonding to bone through a hydroxycarbonate apatite (HCA) surface layer but the release of active ions is more important for bone regeneration
6 μg ml− 1 cobalt was measured in solution at 21 d for 2Co-A, while 5 and 3.5 μg ml− 1 were measured for 5Co-A and 5Co-B, respectively. 2Co-B, 5Co-A and 5Co-B all delivered an initial burst release of cobalt ions, over the first 2 h of dissolution, after which there was an overall decrease up to 21 d. 2Co-A was the only glass in which an increase in cobalt was measured between 1 h and 21 d, with the increase being around 30%, it was approximately constant from 2 d onwards
Cobalt containing silicate glass compositions were designed to avoid the formation of a HCA layer following incubation in Simulated Body Fluid (SBF) buffer, and yet retain the ability to allow cobalt ions to be released
Summary
Bioactive glasses are traditionally associated with bonding to bone through a hydroxycarbonate apatite (HCA) surface layer but the release of active ions is more important for bone regeneration They are being used to deliver ions for soft tissue applications, wound healing. The aim here was to develop new bioactive glass compositions designed to be scaffold materials to locally deliver pro-angiogenic cobalt ions, at a controlled rate, without forming an HCA layer, for wound healing applications. Bioactive glasses are those that can provoke a specific beneficial biological response when implanted [1,2,3]. HCA formation may inhibit haemostasis [22] and calcium deposits have been shown to impede healing of leg ulcers [23,24,25]
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