Synthesis and characterization of titanium dioxide decorated mesoporous silica nanoparticles for bone tissue engineering

Abstract

Bone tissue engineering has emerged as an alternative to overcome the problems associated with the commonly used surgical interventions for correcting bone defects such as donor site morbidity, multiple surgeries, risk of post-operative infections, etc. Central to the theme of bone tissue engineering is theuse of osteoconductive and osteoinductive scaffolds in conjunction with cells and growth factors that promote proper bone remodelling. While the use of scaffolds has been moderately successful in ensuring proper bone growth, greater improvement in their osteoconductive potential still remains to be sought. In addition, the requirement for sustained release of therapeutic molecules at the site of implantation and prevention of bacterial infection remains a challenge in bone tissue engineering. Porous nanoparticles have long been exploited for drug delivery application due to their high drug loading capacity and sustained release profile. Keeping this perspective in mind, the study was aimed at utilizing the osteoconductive properties of mesoporous silica nanoparticles and high porosity of the mesopores for tailored loading and delivery of drug into bone cells. Furthermore, TiO2 was decoratedon the surface of mesoporous silica nanoparticles to impart anti-microbial and immune-modulatory properties to the system as desired in bone tissue engineering. Mesoporous silica nanoparticles (MSN) were synthesized using a surfactant templating method followed by decoration of TiO2 on the surface of the particles. TiO2 decorated mesoporous silica nanoparticle(MST)was prepared by controlled hydrolysis of titanium (IV) butoxide was in methanolic medium in presence of MSN suspension. An osteogenic differentiation inducing corticosteroid drug, dexamethasone was loaded into the mesopores by a simple adsorption-based method. We observed a three-fold increase in drug loading efficiency than what is currently reported in literature for MSN. The as synthesized MSN and MST was thoroughly characterized by FESEM, TEM, XRD, DLS, DRS and zeta potential analysis. Microscopic characterizations revealed that the size of the synthesized nanoparticles was less than 150 nm. XRD analysis revealed that the TiO2 decorated onto the surface of MSN was of the anatase form which possesses intrinsicreactive oxygen species (ROS) generation capacity, which was further confirmed by band-gap analysis and chemical ROS analysis. MG-63 cells were exposed to the synthesized nanoparticles at a definite concentration and their effects were assessed through various cellular assays, such as MTT, PI based live-dead assay, flow cytometry-based ROS and cell cycle analysis to establish that the nanoparticles could support cell adhesion and proliferation without posing any toxicity. Also, the ability of the nanoparticles to induce nodule formation was established through microscopic analysis. The particles were found non-immunogenic with mild immunomodulatory properties when tested against murine macrophage cells.Altogether the study confirms, that the biological per formance of TiO2 decorated MSN is comparable with pure MSN but drug loading capacity and anti-microbial property are better with respect to pure MSN.