One-Pot Sol-Gel Synthesis of Sr/Ca-Doped Silica Nanoparticles for Osteogenic Therapy in Osteoporosis

Alessandra Pinna^1,2*Juan C Palomeque Chávez²Ali A Mohammed²Sareh Aghajanpour¹Siwei Li^2,3Stefano Enzo⁴Nicole L Kelly⁵Gwilherm Kerherve²Alexandra E Porter²John Hanna⁵Julian R. Jones²

• ¹University of Surrey, Guildford, United Kingdom
• ²Imperial College London, London, United Kingdom
• ³Visiting Specialist Services Academy Ltd, London, United Kingdom
• ⁴Universita degli Studi di Sassari, Sassari, Italy
• ⁵University of Warwick, Coventry, United Kingdom

Strontium-and calcium-doped mesoporous bioactive glass nanoparticles (BGNPs) represent a promising strategy to tackle osteoporosis by combining bioactive bone-regenerative properties with controlled release of therapeutic ions. This study pursued two main objectives: (i) to optimize a one-step sol-gel (modified Stöber) synthesis method to control BGNP size and morphology by altering the solvent system, and (ii) to assess how these physicochemical variations affect the response of pre-osteoblasts (MC3T3-E1). BGNPs were synthesized in either pure water or a 1:1 volume ratio ethanol/water mixture. The inclusion of ethanol produced smaller, uniform spherical particles (74 ± 5 nm), while synthesis in water alone yielded significantly larger particles (224 ± 42 nm). X-ray photoelectron spectroscopy and ²⁹Si MAS NMR analysis confirmed that Sr²⁺ and Ca²⁺ were incorporated primarily as network modifiers, maintaining an amorphous silicate structure without forming crystalline silicate phases. Cytotoxicity assays indicated a size-dependent effect: the larger particles decreased cell viability at 1 μg mL⁻¹, whereas both particle sizes were biocompatible at 0.1 μg mL⁻¹. At this lower, non-toxic concentration, BGNPs enhanced alkaline phosphatase activity, promoted osteogenic differentiation, and exhibited antioxidant activity by neutralizing tert-butyl hydroperoxide-induced free radicals. Overall, these results demonstrate that solvent-controlled synthesis effectively modulates BGNP size without disrupting their silicate framework, and that properly sized Sr/Ca-doped BGNPs support osteogenic activity, highlighting their potential as advanced therapeutic agents for osteoporosis treatment.