Unraveling the role of calcium in the osteogenic behavior of mesoporous bioactive glass nanoparticles

Abstract

The use of bioactive materials has emerged as a promising strategy to circumvent bone-related diseases. Because of their chemical composition, calcium-containing bioactive glasses, including mesoporous bioactive glass nanoparticles (nMBG), have long demonstrated their bone regeneration features. In this work, SiO₂-CaO nMBG were synthesized varying Si/Ca ratio from 10 % to 40 % to explore the role of Ca in the osteogenic properties of such materials. We have performed an in-depth physicochemical and biological evaluation of samples by TEM, FTIR, adsorption nitrogen and solid state NMR, revealing that increasing calcium weakens the silica network and consequently, the osteogenic properties. In addition, we have evaluated the protein corona in human serum, obtaining varying protein patterns depending on the Si/Ca ratio and the incubation time. The cellular studies have shown that only certain amounts of calcium up-regulate the osteogenic differentiation, although exceeding such concentrations does not provide improved effects. Finally, All Ca-containing samples promoted calcium phosphate mineralization in biological fluids, while those with higher Si/Ca ratios enhanced significantly hMSC and hOB mineralization. Calcium also modulated hMSC gene expression, with samples containing up to 20 % calcium up-regulating OC and RUNX2. Furthermore, nMBG exhibited immunomodulatory properties, inducing a shift toward the M2 reparative phenotype. Overall, this comprehensive study highlights the crucial role of calcium in osteogenic responses, demonstrating that calcium quantity alone does not surpass the importance of structural and compositional quality in nanosized MBG.