Bioactive glasses are of interest in regenerative medicine as they can incorporate ions beneficial for tissue repair and release these into aqueous environments as the glass degrades. To date, bioactive glasses have been primarily used for bone regeneration, however they have also shown promise in soft tissue applications, such as wound healing.
When a wound forms, a cascade of events occur to repair the damaged skin. If healing is impaired, for example in diabetic patients, a chronic wound can form, which does not heal in a predictable manner. The Hypoxia Inducible Factor (HIF) pathway regulates the expression of genes involved in adaption to hypoxia, such as those involved in angiogenesis, and local activation of this pathway can promote the healing of diabetic wounds.
Cobalt is known to activate the HIF pathway, and in this thesis, cobalt bioactive glasses were investigated for the first time in wound healing applications. New melt-derived glass compositions were designed, which could degrade and release cobalt ions in aqueous environments, without the formation of crystalline hydroxycarbonate apatite.
Glass particles are not suitable for direct application to a wound bed, and therefore the designed glasses were developed into composites by electrospinning, and into fibres by laser spinning. These formats were able to release cobalt ions and activate the HIF pathway in vitro, causing a functional response measured by an increased expression of Vascular Endothelial Growth Factor (VEGF). By comparing a single composition with and without cobalt, it was shown that the cobalt bioactive glass fibres caused a synergistic effect on HIF-1α stabilisation and VEGF expression, which could not be replicated by supplementing cell culture media with cobalt. Overall the work presented in this thesis shows the potential for the designed cobalt bioactive glass compositions and formats to be used to promote the healing of chronic wounds.