Magnesium- and cerium-doped mesoporous bioactive glasses as multifunctional platform for polyphenol delivery and enhanced antioxidant activity

Mesoporous bioactive glasses (MBGs) represent a promising class of materials for biomedical applications due to their large surface area, high pore volume, and tuneable composition.Due to such surface properties, this work explores for the first time the possibility of exploiting MBGs as a multifunctional platform boosting bioactivity by magnesium and cerium co-doping, as well as a delivery of polyphenols, with the aim of tuning inflammation in situ.Accordingly, four MBG compositions with varying Mg and Ce contents were synthesized via the sol–gel method and loaded with three pure polyphenols: 3-hydroxyflavone, quercetin, and morin hydrate. The multiparametric characterization confirmed the amorphous nature of all glasses, high specific surface area (SSA, > 300 m2/g), in vitro bioactivity in simulated body fluid (SBF), significant antioxidant activity, and cytocompatibility toward human bone marrow-derived mesenchymal stem cells (hBMSCs), as well. In particular, Ce/Mg co-doping notably enhanced catalase (CAT)-like activity, while polyphenol loading, particularly with quercetin, markedly improved superoxide dismutase (SOD)-mimetic activity. Similarly, quercetin functionalization demonstrated strong scavenging activity, protecting hBMSCs from the intracellular accumulation of toxic reactive oxygen species (ROS) compared with bulk controls when oxidative stress was induced with H2O2. Moreover, when the pro-inflammatory cascade was induced by interleukin administration, the presence of quercetin effectively promoted the upregulation of the anti-inflammatory genes TGF-β1 and IL-10, demonstrating a strong ability to modulate the inflammation in situ. Taken together, these findings highlight the potential of Ce/Mg co-doped MBGs as bioactive multifunctional carriers for the delivery of antioxidant biomolecules.