INTRODUCTION: A critical step preceding the potential biomedical application of nanoparticles is the evaluation of their immunomodulatory effects. Such nanoparticles are expected to enter the bloodstream where they can be recognized and processed by circulating monocytes. Despite the required biocompatibility, this interaction can affect intracellular homeostasis and modulate physiological functions, particularly inflammation. This study focuses on titanium dioxide (TiO2) as an example of relatively low cytotoxic nanoparticles with potential biomedical use and aims to evaluate their possible modulatory effects on the inflammasome-based response in human primary monocytes. METHODS: Monocyte viability, phenotypic changes, and cytokine production were determined after exposure to TiO2 (diameter, 25 nm; P25) alone. In the case of the modulatory effects, we focused on NLRP3 activation. The production of IL-1β and IL-10 was evaluated after (a) simultaneous activation of monocytes with bacterial stimuli muramyl dipeptide (MDP), or lipopolysaccharide (LPS), and TiO2 (co-exposure model), (b) prior activation with TiO2 alone and subsequent exposure to bacterial stimuli MDP or LPS. The differentiation of TiO2-treated monocytes into macrophages and their polarization were also assessed. RESULTS: The selected TiO2 concentration range (30-120 μg/mL) did not induce any significant cytotoxic effects. The highest dose of TiO2 promoted monocyte survival and differentiation into macrophages, with the M2 subset being the most prevalent. Nanoparticles alone did not induce substantial production of inflammatory cytokines IL-1β, IL-6, or TNF-α. The immunomodulatory effect on NLRP3 depended on the type of costimulant used. While co-exposure of monocytes to MDP and TiO2 boosted NLRP3 activity, co-exposure to LPS and TiO2 inhibited NLRP3 by enhancing IL-10 release. The inhibitory effect of TiO2 on NLRP3 based on the promotion of IL-10 was confirmed in a post-exposure model for both costimulants. CONCLUSION: This study confirmed a non-negligible modulatory effect on primary monocytes in their inflammasome-based response and differentiation ability.
- MeSH
- Acetylmuramyl-Alanyl-Isoglutamine pharmacology MeSH
- Cell Differentiation drug effects MeSH
- Cytokines metabolism MeSH
- Inflammasomes drug effects MeSH
- Interleukin-10 metabolism MeSH
- Interleukin-1beta metabolism MeSH
- Metal Nanoparticles chemistry toxicity MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Lipopolysaccharides * pharmacology MeSH
- Macrophages drug effects MeSH
- Monocytes * drug effects MeSH
- Nanoparticles chemistry toxicity MeSH
- NLR Family, Pyrin Domain-Containing 3 Protein * metabolism MeSH
- Titanium * chemistry pharmacology toxicity MeSH
- Cell Survival * drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Targeted alpha therapy (TAT) is an effective option for cancer treatment. To maximize its efficacy and minimize side effects, carriers must deliver radionuclides to target tissues. Most of the nuclides used in TAT decay via the alpha cascade, producing several radioactive daughter nuclei with sufficient energy to escape from the original carrier. Therefore, studying these daughter atoms is crucial in the search for new carriers. Nanoparticles have potential as carriers due to their structure, which can prevent the escape of daughter atoms and reduce radiation exposure to non-target tissues. This work focuses on determining the released activity of 221Fr and 213Bi resulting from the decay of 225Ac labelled TiO2 nanoparticles. RESULTS: Labelling of TiO2 nanoparticles has shown high sorption rates of 225Ac and its progeny, 221Fr and 213Bi, with over 92 % of activities sorbed on the nanoparticle surface for all measured radionuclides. However, in the quasi-dynamic in vitro system, the released activity of 221Fr and 213Bi is strongly dependent on the nanoparticles concentration, ranging from 15 % for a concentration of 1 mg/mL to approximately 50 % for a nanoparticle concentration of 10 μg/mL in saline solution. The released activities of 213Bi were lower, with a maximum value of around 20 % for concentrations of 0.05, 0.025, and 0.01 mg/mL. The leakage of 225Ac and its progeny was tested in various biological matrices. Minimal released activity was measured in saline at around 10 % after 48 h, while the maximum activity was measured in blood serum and plasma at 20 %. The amount of 225Ac released into the media was minimal (<3 %). The in vitro results were confirmed in a healthy mouse model. The difference in %ID/g was clearly visible immediately after dissection and again after 6 h when 213Bi reached equilibrium with 225Ac. CONCLUSION: The study verified the potential release of 225Ac progeny from the labelled TiO2 nanoparticles. Experiments were performed to determine the dependence of released activity on nanoparticle concentration and the biological environment. The results demonstrated the high stability of the prepared 225Ac@TiO2 NPs and the potential release of progeny over time. In vivo studies confirmed our hypothesis. The data obtained suggest that the daughter atoms can escape from the original carrier and follow their own biological pathways in the organism.
- MeSH
- Actinium * chemistry MeSH
- Isotope Labeling MeSH
- Mice MeSH
- Nanoparticles * chemistry MeSH
- Radioisotopes chemistry MeSH
- Titanium * chemistry MeSH
- Tissue Distribution MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: A comparison of fusion rates and clinical outcomes of instrumented transforaminal interbody fusion (TLIF) between polyetheretherketone (PEEK) and titanium-coated PEEK (Ti-PEEK) cages is not well documented. METHODS: A single-centre, prospective, randomised study included patients who underwent one-level TLIF between L3-S1 segments. Patients were randomised into one of two groups: TLIF surgery with the PEEK cage and TLIF surgery with the Ti-PEEK cage. Clinical results were measured. All patients were assessed by repeated X-rays and 3D CT scans. Cage integration was assessed using a modified Bridwell classification. The impact of obesity and smoking on fusion quality was also analysed. Patients in both groups were followed up for 2 years. RESULTS: Altogether 87 patients were included in the study: of these 87 patients, 81 (93.1%) completed the 2-year follow-up. A significant improvement in clinical outcome was found in the two measurements scales in both groups (RM: p = 0.257, VAS: p = 0.229). There was an increase in CobbS and CobbL angle in both groups (p = 0.172 for CobbS and p = 0.403for CobbL). Bony fusion was achieved in 37 of 40 (92.5%) patients in the TiPEEK group and 35 of 41 (85.4%) in the PEEK group (p = 0.157). Cage subsided in 2 of 40 patients (5%) in the TiPEEK group and 11 of 41 (26.8%) in the PEEK group (p = 0.007). Body mass index > 30 and smoking were not predictive factors of bony fusion achievement. CONCLUSION: There is no significant advantage of TiPEEK cages over PEEK cages in clinical outcome and fusion rate 2 years after surgery.
- MeSH
- Lumbar Vertebrae surgery MeSH
- Benzophenones * MeSH
- Spinal Fusion * methods MeSH
- Ketones MeSH
- Humans MeSH
- Polyethylene Glycols MeSH
- Polymers * MeSH
- Prospective Studies MeSH
- Titanium * MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
Materials used for orthopedic implants should not only have physical properties close to those of bones, durability and biocompatibility, but should also exhibit a sufficient degree of antibacterial functionality. Due to its excellent properties, titanium is still a widely used material for production of orthopedic implants, but the unmodified material exhibits poor antibacterial activity. In this work, the physicochemical characteristics, such as chemical composition, crystallinity, wettability, roughness, and release of Ti ions of the titanium surface modified with nanotubular layers were analyzed and its antibacterial activity against two biofilm-forming bacterial strains responsible for prosthetic joint infection (Staphylococcus aureus and Pseudomonas aeruginosa) was investigated. Electrochemical anodization (anodic oxidation) was used to prepare two types of nanotubular arrays with nanotubes differing in dimensions (with diameters of 73 and 118 nm and lengths of 572 and 343 nm, respectively). These two surface types showed similar chemistry, crystallinity, and surface energy. The surface with smaller nanotube diameter (TNT-73) but larger values of roughness parameters was more effective against S. aureus. For P. aeruginosa the sample with a larger nanotube diameter (TNT-118) had better antibacterial effect with proven cell lysis. Antibacterial properties of titanium nanotubular surfaces with potential in implantology, which in our previous work demonstrated a positive effect on the behavior of human gingival fibroblasts, were investigated in terms of surface parameters. The interplay between nanotube diameter and roughness appeared critical for the bacterial fate on nanotubular surfaces. The relationship of nanotube diameter, values of roughness parameters, and other surface properties to bacterial behavior is discussed in detail. The study is believed to shed more light on how nanotubular surface parameters and their interplay affect antibacterial activity.
- MeSH
- Anti-Bacterial Agents * pharmacology chemistry MeSH
- Biofilms drug effects growth & development MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Nanotubes * chemistry MeSH
- Surface Properties * MeSH
- Pseudomonas aeruginosa * drug effects MeSH
- Staphylococcus aureus * drug effects MeSH
- Titanium * chemistry pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Biocompatible Materials therapeutic use MeSH
- Adult MeSH
- Esthetics, Dental MeSH
- Prosthesis Implantation methods MeSH
- Ceramics * therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Titanium therapeutic use MeSH
- Zirconium MeSH
- Dental Implants * MeSH
- Dental Materials therapeutic use MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Dental Implantation * methods MeSH
- Ceramics therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Dental Abutments MeSH
- Titanium therapeutic use MeSH
- Zirconium therapeutic use MeSH
- Dental Implants MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Review MeSH
Microbial colonization on the titanium condenser material (TCM) used in the cooling system leads to biofouling and corrosion and influences the water supply. The primary investigation of the titanium condenser was infrequently studied on characterizing biofilm-forming bacterial communities. Different treatment methods like electropotential charge, ultrasonication, and copper coating of titanium condenser material may influence the microbial population over the surface of the titanium condensers. The present study aimed to catalog the primary colonizers and the effect of different treatment methods on the microbial community. CFU (1.7 × 109 CFU/mL) and ATP count (< 5000 × 10-7 relative luminescence units) showed a minimal microbial population in copper-coated surface biofilm as compared with the other treatments. Live and dead cell result also showed consistency with colony count. The biofilm sample on the copper-coated surface showed an increased dead cell count and decreased live cells. In the metagenomic approach, the microbiome coverage was 10.06 Mb in samples derived from copper-coated TCM than in other treated samples (electropotential charge-17.94 Mb; ultrasonication-20.01 Mb), including control (10.18 Mb). Firmicutes preponderate the communities in the biofilm samples, and Proteobacteria stand next in the population in all the treated condenser materials. At the genus level, Lactobacillaceae and Azospirillaceae dominated the biofilm community. The metagenome data suggested that the attached community is different from those biofilm samples based on the environment that influences the bacterial community. The outcome of the present study depicts that copper coating was effective against biofouling and corrosion resistance of titanium condenser material for designing long-term durability.
We analyzed gene expression in THP-1 cells exposed to metal-based nanomaterials (NMs) [TiO2 (NM-100), ZnO (NM-110), SiO2 (NM-200), Ag (NM-300 K)]. A functional enrichment analysis of the significant differentially expressed genes (DEGs) identified the key modulated biological processes and pathways. DEGs were used to construct protein-protein interaction networks. NM-110 and NM-300 K induced changes in the expression of genes involved in oxidative and genotoxic stress, immune response, alterations of cell cycle, detoxification of metal ions and regulation of redox-sensitive pathways. Both NMs shared a number of highly connected protein nodes (hubs) including CXCL8, ATF3, HMOX1, and IL1B. NM-200 induced limited transcriptional changes, mostly related to the immune response; however, several hubs (CXCL8, ATF3) were identical with NM-110 and NM-300 K. No effects of NM-100 were observed. Overall, soluble nanomaterials NM-110 and NM-300 K exerted a wide variety of toxic effects, while insoluble NM-200 induced immunotoxicity; NM-100 caused no detectable changes on the gene expression level.
- MeSH
- Heme Oxygenase-1 MeSH
- Interleukin-8 metabolism genetics MeSH
- Metal Nanoparticles toxicity MeSH
- Humans MeSH
- Protein Interaction Maps * drug effects MeSH
- Nanostructures toxicity MeSH
- Silicon Dioxide toxicity MeSH
- Zinc Oxide toxicity chemistry MeSH
- Silver * toxicity MeSH
- THP-1 Cells MeSH
- Titanium * toxicity MeSH
- Activating Transcription Factor 3 genetics metabolism MeSH
- Transcriptome drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Diamond-like carbon (DLC) layers are known for their high corrosion and wear resistance, low friction, and high biocompatibility. However, it is often necessary to dope DLC layers with additional chemical elements to strengthen their adhesion to the substrate. Ti-DLC layers (doped with 0.4, 2.1, 3.7, 6.6, and 12.8 at.% of Ti) were prepared by dual pulsed laser deposition, and pure DLC, glass, and polystyrene (PS) were used as controls. In vitro cell-material interactions were investigated with an emphasis on cell adhesion, proliferation, and osteogenic differentiation. We observed slightly increasing roughness and contact angle and decreasing surface free energy on Ti-DLC layers with increasing Ti content. Three-week biological experiments were performed using adipose tissue-derived stem cells (ADSCs) and bone marrow mesenchymal stem cells (bmMSCs) in vitro. The cell proliferation activity was similar or slightly higher on the Ti-doped materials than on glass and PS. Osteogenic cell differentiation on all materials was proved by collagen and osteocalcin production, ALP activity, and Ca deposition. The bmMSCs exhibited greater initial proliferation potential and an earlier onset of osteogenic differentiation than the ADSCs. The ADSCs showed a slightly higher formation of focal adhesions, higher metabolic activity, and Ca deposition with increasing Ti content.
