Thiol-Functionalized, Antioxidant, and Osteogenic Mesoporous Silica Nanoparticles for Osteoporosis.

Osteoporosis is a chronic bone disorder characterized by decreased bone mass, leading to brittle bones and fractures. Oxidative stress has been identified as the most profound trigger for the initiation and progression of osteoporosis. Current treatment strategies do not induce new bone formation and fail to address a high level of reactive oxygen species (ROS). Mesoporous silica nanoparticles (MSNs) have been explored in bone tissue regeneration owing to their inherent osteogenic property, but they lack antioxidant and cell adhesion properties, required in such applications. We have developed thiolated, bioactive mesoporous silica nanoparticles (MSN-SH) to address this challenge. MSNs were fabricated using the Stöber method, and 11% of the surface was functionalized post-synthesis with thiol groups using MPTMS to obtain MSN-SH. The particle size measured by the dynamic light scattering technique was found to be around 300 nm. The surface morphology was investigated using HR-TEM, and their physical and chemical properties were characterized using various spectroscopic techniques. They exhibited more than 90% antioxidant activity, neutralized ROS formed in cells, and provided protection against ROS-induced cell damage. The cell viability assay in murine osteoblast precursor cells (MC3T3) showed that MSN-SH is cell-proliferative in nature with 140% cell viability. Osteogenic potential was evaluated by measuring the ALP activities, calcium deposition, and gene expression levels of osteogenic markers, such as RUNX2, ALP, OCN, and OPN, and results revealed that MSN-SH increases calcium deposition and induces osteogenesis through upregulation of osteogenic genes and markers without the involvement of any osteogenic supplements. Besides promoting osteogenesis, MSN-SH was found to inhibit osteoclastogenesis. The nanomaterial was found to be regenerative in nature, and it stimulated migration of osteoblast cells and caused a complete wound closure within 48 h. We were able to achieve a multifunctional nanomaterial by simply modifying the surface. MSNs have been explored for bone tissue engineering/osteoporosis as a composite system incorporating metals, like gold and cerium, or as a nanocarrier loaded with growth factors or active drugs. This study offers a simple and economical method to enhance the existing properties of MSNs and impart new activities by a single-step surface modification. It can be concluded that MSN-SH holds promise as a complementary and alternate treatment for osteoporosis along with the standardized therapy.

Cationized silica ceria nanocomposites to target biofilms in chronic wounds.

Altered wound healing is a major challenge faced by both developed and developing nations. Biofilm formation has been identified as one of the causative factors for the progression of chronic wounds. The spread of biofilm is controlled by inhibiting the biofilm formation or disrupting the mature biofilm. Functional nanomaterials/enzymes with antimicrobial effects, such as metal oxides, rare earth metals, and carbon nanoparticles have been investigated to treat biofilm and overcome the drawbacks associated with the antibiotic therapy. Cerium oxide nanoparticles (CNPs) have drawn significant attention as a promising antimicrobial agent owing to their antibacterial, enzyme-mimetic, and crystalline properties but they suffer from poor colloidal stability and dispersity in an aqueous environment and size-dependent function. In this work, we have developed a functionalized silica ceria nanocomposite (FSC), as an antibiotic-free system, to treat biofilms. The FSC possesses a high surface area of mesoporous silica nanoparticles (MSNs) combined with the intrinsic antibacterial activity of cerium oxide for biofilm inhibition. The nanocomposite was fabricated using silica and ceria precursors, and it exhibited a high surface area of 436 m2/g and an average particle size of around 450 nm. The physical and chemical properties of nanocomposite were characterized using FTIR, XRD, UV-Vis, BET, EDX, and XPS analysis. It exhibited a potent antioxidant activity (86%), positive haloperoxidase mimetic property, and broad-spectrum antibacterial activities. It showed 99.9% inhibition against S. aureus (Gram-positive) and 81% inhibition against E. coli (Gram-negative) within 12 and 24 h along with the significant inhibition of biofilm formation (80%) as well as the disruptive effect against the established biofilm (77%) of S. aureus. Cell viability assays indicated the proliferative nature of composite in normal basal conditions and increased cell viability (97%) in the presence of oxidative stress. Despite being a cationic nanomaterial, it showed a good hemocompatibility against human blood and caused complete wound closure in mouse fibroblast cell line within 24 h. The functionalized silica ceria nanocomposite developed has a strong potential in chronic wound healing applications.