Magnesium and strontium-enriched bioactive glasses: superior biocompatibility and angiogenesis, beyond the gold standard

Bioactive glasses (BGs) have garnered attention for their potential as transformative bone substitutes in regenerative medicine. BGs exert their effects through the dissolution of active ions that can stimulate osteoprogenitors and endothelial cells in the osteogenic process. In this paper, two recent BGs formulations (BGMS10 and Bio_MS), enriched in Sr and Mg ions and with extremely high crystallization temperature, were evaluated. The effects of such BGs on endothelial cell adhesion, viability, and proliferation were analyzed both in the actual presence of BGs and in indirect settings, to determine the impact of ionic dissolution products. The novel BGs were compared to 45S5 Bioglass (R), demonstrating a significantly higher biocompatibility and viability of cells grown onto the two novel formulations. Then, the angiogenic potential was evaluated via the Chorio-Allantoic Membrane (CAM) assay which, acting as natural bioreactor, simulates the in vivo conditions. All the BGs demonstrated to be significantly pro-angiogenic compared to controls, showing a significant upregulation of genes with a key role in angiogenic pathways. These observations were consistent with the tissue histological evaluations, which displayed high biocompatibility of BGMS10 and Bio_MS, and a remarkable proliferation of CAM tissues with no inflammatory reactions. In conclusion, our results show that these novel formulations are extremely effective in promoting cell adhesion, proliferation and angiogenesis, which are fundamental for the complex process of healing.