Effect of magnesium-degradation products and hypoxia on the angiogenesis of human umbilical vein endothelial cells

Abstract

Biodegradable magnesium (Mg) metals have been applied in orthopaedic and stent applications due to their biodegradability, bioabsorbability and adaptability to tissue regeneration. However, further investigations are still needed to understand how angiogenesis will respond to high concentrations of Mg and oxygen content differences, which are vital to vascular remodelling and bone fracture regeneration or tissue healing. Human primary endothelial cells were exposed to various concentrations (2-8 mM) of extracellular Mg degradation products under either hypoxia or normoxia. Increased proliferation was measured with Mg extracts under hypoxia but not under normoxia. Under normoxia and with Mg extracts, HUVEC migration exhibited a bell-shaped curve. The same pattern was observed with VEGFB expression, while VEGFA was constantly downregulated. Under hypoxia, migration and VEGFA levels remained constant; however, VEGFB was upregulated. Similarly, under normoxia, tube formation as well as VEGFA and VEGFB levels were downregulated. Nevertheless, under hypoxia, tube formation remained constant while VEGFA and VEGFB levels were upregulated. These results suggest that Mg extracts did not interfere with angiogenesis under hypoxia. STATEMENT OF SIGNIFICANCE: Neoangiogenesis, mediated by (e.g.) hypoxia, is a key factor for proper tissue healing Thus, effect of Mg degradation products under either hypoxia or normoxia on angiogenesis were investigated. Under normoxia and increased Mg concentrations, a general negative effect was measured on early (migration) and late (tubulogenesis) angiogenesis. However, under hypoxia, this effect was abolished. As magnesium degradation is an oxygen-dependant process, hypoxia condition may be a relevant factor to test material cytocompatibility in vitro.

Keywords: Angiogenesis; Hypoxia; Magnesium; Normoxia; Primary endothelial cell.