High VEGF Secretion Using Co and B Co-doped Bioactive Mesoporous Glass Nanoparticles for Enhanced Angiogenesis

This investigation presents a novel approach to engineering mesoporous bioactive glass nanoparticles (MBGNs) through selective ion doping. This method can significantly potentiate their physicochemical properties and biological performance. We elucidate the effects of boron (B) and cobalt (Co) doping, individually and in combination, on MBGNs' structural, functional, and biocompatible characteristics. Using microemulsion-assisted sol-gel synthesis, we fabricated MBGNs with sizes ranging from 150 to 250 nm and shapes that shifted from spherical to more irregular shapes upon co-doping, as observed by SEM and TEM. We assessed the materials' amorphous nature and molecular structure through XRD and FTIR, respectively, noting the preservation of bioactivity-associated Si-O-Si groups. This can influence the nucleation and growth of the mineral phases similar to those found in natural tissues, forming a bioactive coating on the material surface. Nitrogen adsorption-desorption isotherms confirmed a mesoporous structure with increased specific surface area upon co-doping. The release behavior of Ca and Si in simulated body fluids studied by ICP-OES indicated alterations after adding Co and B, modifying their release kinetics. Bone regeneration relies on osteogenesis and vascular network formation for nutrient and oxygen supply. This study highlights the synergistic effect of B and Co co-doping, enhancing both angiogenesis and osteogenesis beyond single-ion doping. Biocompatibility studies with MG-63 and HDFa cell lines indicated that B enhanced cell viability, while the viability effect of Co was concentration-dependent. Cytotoxicity was assessed through lactate dehydrogenase (LDH) assays and is shown in high concentrations in the case of reference and B-doped sample, which was significantly reduced in the case of co-doped material. The newly developed nanoparticles showed a 10-fold increase in vascular endothelial growth factor (VEGF) secretion compared to the control sample (<i>p</i> < 0.05, one-way ANOVA), as determined by enzyme-linked immunosorbent assay (ELISA) in treated cells. Based on present results, the co-doped system shows a strong potential impact on angiogenesis with no effect on cell cytotoxicity.