Ion-Containing Mesoporous Silica-Based Nanomaterials for Bone Regeneration: Emphasis on In Situ Co-Condensation, Multifunctional Bioactivity, and Spatiotemporal Delivery

Bone defects remain difficult to treat because conventional grafting approaches may cause infection, inflammation, donor-site morbidity, or graft rejection. Mesoporous silica nanoparticles (MSNs) have emerged as versatile nanomaterials for drug delivery owing to their large surface area, tunable pore structure, high loading capacity, and readily modifiable surfaces. However, conventional MSNs are relatively bioinert and provide limited direct stimulation of bone regeneration. Incorporating therapeutic metal ions into the silica framework through in situ co-condensation can improve their biological activity while retaining their drug-delivery advantages. This review highlights recent advances in ion-doped MSNs as multifunctional delivery systems for bone regeneration, focusing on their osteogenic, angiogenic, anti-inflammatory, and antibacterial effects. The review discusses how ion doping influences particle structure, biodegradation, drug loading, and release behavior and the potential of single- and multiple-ion systems to provide complementary or, where experimentally demonstrated, synergistic therapeutic effects. Particular attention is given to controlled and spatiotemporal delivery strategies designed to match the sequential phases of bone healing. Future research should improve synthetic reproducibility, establish ion-specific therapeutic windows, integrate stimuli-responsive release mechanisms, and confirm long-term safety and efficacy in clinically relevant animal models.