Silver‐Doped Mesoporous Bioactive Glass Nanoparticles With Core–Shell Architecture: Enhanced In Vitro Bioactivity, Antibacterial Efficacy, and Biocompatibility

Orthopedic biomaterials must both prevent infection and support bone regeneration. To achieve both outcomes with bioactive glass nanoparticles (BGNs), rational nanoarchitectural design is required to decouple and tune silver-ion (Ag⁺) and calcium-ion (Ca²⁺) release, balancing antibacterial efficacy with osteogenic compatibility. Herein, we synthesized four BGN types via a modified sol-gel route: solid spheres, Ag-doped solid spheres, core-shell mesoporous BGNs, and Ag-doped core-shell mesoporous BGNs. Core-shell architectures were generated by alkaline etching followed by calcium impregnation, and silver was introduced during synthesis. Comprehensive characterization (scanning/transmission electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy) confirmed homogeneous amorphous glass networks with spatially distinct Ca and Ag distributions in the mesoporous particles. Brunauer-Emmett-Teller analysis showed high-surface-area mesoporous BGNs (≈860 m²/g) versus solid spheres (≈17 m²/g), with markedly greater pore volume. Inductively coupled plasma mass spectrometry revealed sustained Ag⁺ and Ca²⁺ release over 21 days within sub-microgram-per-milliliter levels, consistent with the core-shell design. These physicochemical features translated into superior biological performance: Ag-doped mesoporous BGNs accelerated mineralization in simulated body fluid, exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus and Escherichia coli, and supported the viability and osteogenic differentiation of human mesenchymal stem cells. In ovo biocompatibility testing found no vascular irritation in the Hen's Egg Test on the Chorioallantoic Membrane (HET-CAM). Altogether, nanostructural tuning, particularly combining mesoporosity with a core-shell architecture, can optimize ion-release behavior and biological function in BGNs, advancing multifunctional nanoglasses for regenerative and antimicrobial applications.