Association of Non-Bridging Oxygen with Cytocompatibility in Cerium and Cobalt Codoped 58S Bioglass

58S-Bioactive glass (bioactive glass (BG)) exhibits exceptional osteointegration (bioactivity), making it highly suitable for applications such as dental implants, bone healing, and tissue regeneration, but lacks antibacterial properties. In the current study, cobalt and cerium are used as potential dopants to stimulate osteoblast-like MG-63 and NIH 3T3 cells, inhibit growth of Escherichia coli and Staphylococcus aureus, while exhibiting enhanced mechanical properties. Doping of Ce and Co into 58S-BG induced structural changes, evidenced by the shift in Si 2p and O 1s spectra to lower binding energy, is associated with an enhanced nonbridging oxygen. Highly dense (∼98%) 2.5Ce5CoBG spark plasma sintered (SPS, crystallinity <5%) pellets exhibit a nanohardness of ∼5.61 GPa (↑ by ∼124%) and Young’s modulus of ∼75 GPa (↑ by ∼74%) as compared to that of BG. All samples (SPS pellets) showed in vitro bioactivity with a thick layer of apatite after 7 days, confirmed by scanning electron microscopy (SEM) and X-ray diffraction. Additionally, 2.5Ce5CoBG significantly inhibited bacterial growth, reducing viability by ∼34.5% and ∼52.2% and adhesion by ∼92.7% and ∼94.2% for S. aureus and E. coli, respectively. Even after 48 h of incubation, an effective antibacterial response was evident in SEM images, showing pronounced cytoplasmic membrane damage/rupture compared to 58S BG, thereby, confirming the well-established antibacterial role of Co doping. Doped (Ce, Co) BG nanoparticles exhibit enhanced cell viability of ∼125% for a 1% extract of 2.5Ce5CoBG-NPs compared to that of the control. Furthermore, enhanced cell response was observed for 2.5Ce5CoBG (∼11-fold increase in cell count as compared to BG), an aspect ratio of ∼3.3, filopodial extensions reaching ∼39 μm, and substantial extracellular matrix deposition complemented with pronounced stress fibers formed that were linked to focal adhesion sites, as evidenced by fluorescence microscopy. 2.5Ce5CoBG enhanced cell adhesion, proliferation, and growth; reduced bacterial adhesion and viability; and augmented mechanical properties, suggesting its potential use for bone replacement applications.