Hypoxia-mimicking bioactive glass/collagen glycosaminoglycan composite scaffolds to enhance angiogenesis and bone repair.
Quinlan E., Partap S., Azevedo MM., Jell G., Stevens MM., O'Brien FJ.
One of the biggest challenges in regenerative medicine is promoting sufficient vascularisation of tissue-engineered constructs. One approach to overcome this challenge is to target the cellular hypoxia inducible factor (HIF-1α) pathway, which responds to low oxygen concentration (hypoxia) and results in the activation of numerous pro-angiogenic genes including vascular endothelial growth factor (VEGF). Cobalt ions are known to mimic hypoxia by artificially stabilising the HIF-1α transcription factor. Here, resorbable bioactive glass particles (38 μm and 100 μm) with cobalt ions incorporated into the glass network were used to create bioactive glass/collagen-glycosaminoglycan scaffolds optimised for bone tissue engineering. Inclusion of the bioactive glass improved the compressive modulus of the resulting composite scaffolds while maintaining high degrees of porosity (>97%). Moreover, in vitro analysis demonstrated that the incorporation of cobalt bioactive glass with a mean particle size of 100 μm significantly enhanced the production and expression of VEGF in endothelial cells, and cobalt bioactive glass/collagen-glycosaminoglycan scaffold conditioned media also promoted enhanced tubule formation. Furthermore, our results prove the ability of these scaffolds to support osteoblast cell proliferation and osteogenesis in all bioactive glass/collagen-glycosaminoglycan scaffolds irrespective of the particle size. In summary, we have developed a hypoxia-mimicking tissue-engineered scaffold with pro-angiogenic and pro-osteogenic capabilities that may encourage bone tissue regeneration and overcome the problem of inadequate vascularisation of grafts commonly seen in the field of tissue engineering.