Facile post modification synthesis of copper-doped mesoporous bioactive glass with high antibacterial performance to fight bone infection

Successful treatment of infected bone defects caused by multi-drug resistant bacteria (MDR) has become a major clinical challenge, stressing the urgent need for effective antibacterial bone graft substitutes. Mesoporous bioactive glass nanoparticles (MBGNs), a rapidly emerging class of nanoscale biomaterials, offer specific advantages for the development of biomaterials to treat bone infection due to endowed antibacterial features. Herein, we propose a facile post-modification sol-gel strategy to synthesize effective antibacterial MBGNs doped with copper ions (Cu-PMMBGNs). In this strategy, amine functional groups as chelating agents were introduced to premade mesoporous silica nanoparticles (MSNs) which further facilitate the incorporation of high content of calcium (~17 mol%) and copper ions (~8 mol%) without compromising nanoparticle shape, mesoporosity, and homogeneity. The resulting nanoparticles were degradable and showed rapidly induce abundant deposition of apatite crystals on their surface upon soaking in simulated body fluids (SBF) after 3 days. Cu-PMMBGNs exhibited a dose-dependent inhibitory effect on Methicillin-resistant Staphylococcus aureus (MRSA) bacteria, which are common pathogens causing severe bone infections. Most importantly, the nanoparticles containing 5 mol% copper ions at concentrations of 500 and 1000 g.mL -1 showed highly effective antibacterial performance as reflected by a 99.9 % reduction of bacterial viability. Nanoparticles at a concentration of 500 g.mL -1 showed no significant cytotoxicity toward preosteoblast cells (~85-89 % cell viability) compared to the control group. In addition, the nanoscale properties of synthesized Cu-PMMBGNs (~100 nm in size) facilitated their internalization into preosteoblast cells, which highlights their potential as intracellular carriers in combating intracellular bacteria. Therefore, these copper-doped nanoparticles hold strong promise for use as an antibacterial component in antibacterial bone substitutes such as hydrogels, nanocomposites, and coatings.