Bioactive glasses and electrospun composites that release cobalt to stimulate the HIF pathway for wound healing applications

Anu K Solanki, Ferdinand V Lali, Hélène Autefage, Shweta Agarwal, Amy Nommeots-Nomm, Anthony D Metcalfe, Molly M Stevens, Julian R Jones

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
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BACKGROUND: 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 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.

METHODS: New 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.

RESULTS: Dissolution 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).

CONCLUSIONS: The 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.

Original languageEnglish
Article number1
Number of pages16
JournalBiomaterials research
Issue number1
Early online date15 Jan 2021
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
This report is independent research funded by the National Institute for Health Research [Invention for Innovation, Development of hypoxia mimicking materials for soft tissue (wound healing) regenerative medicine product development; II-ES-1010-10094]. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

Publisher Copyright:
© 2021, The Author(s).


  • Bioactive composites
  • Bioactive glass
  • Cobalt
  • HIF pathway
  • Wound healing

ASJC Scopus subject areas

  • Ceramics and Composites
  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering


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