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 μg.mL−1 showed highly effective antibacterial performance as reflected by a 99.9 % reduction of bacterial viability. Nanoparticles at a concentration of 500 μg.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.</p

Characterization of α/β-TCP Based Injectable Calcium Phosphate Cement as a Potential Bone Substitute

Calcium phosphate cements (CPCs) can be a suitable scaffold material for bone tissue engineering because of their osteoconductivity and perfect fit with the surrounding tissue when injected in situ. However, the main disadvantage of hydroxyapatite (HA) forming CPC is its slow degradation rate, which hinders complete bone regeneration. A new approach is to use hydraulic apatite cement with mainly α/β-tricalciumphosphate (TCP) instead of α-TCP. After hydrolysis the α/β-TCP transforms in a partially non-absorbable HA and a completely resorbable β-TCP phase. Therefore, α-TCP material was thermally treated at several temperatures and times resulting in different α/β-TCP ratios. In this experiment, we developed and evaluated injectable biphasic calcium phosphate cements (BCPC) in vitro. Biphasic α/β-TCP powder was produced by heating α-TCP ranging from 1000-11250°C. Setting time and compressive strength of the CPCs were analyzed after soaking in PBS for 6 weeks. Results demonstrated that the phase composition can be controlled by the sintering temperature. Heat treatment of α-TCP, resulted in 100%, 75% and 25% of α-to β-TCP transformation, respectively. Incorporation of these sintered BCP powder into the cement formulation increased the setting time of the CPC paste. Compressive strength decreased with increasing β-TCP content. In this study, biphasic CPCs were produced and characterized in vitro. This injectable biphasic CPC presented comparable properties to an apatitic CPC.</jats:p