Bioactive nano-selenium antagonizes cobalt nanoparticle-mediated oxidative stress via the Keap1-Nrf2-ARE signaling pathway

At present, no effective treatment exists for the clinical toxicity of cobalt nanoparticles (CoNPs, 30 nm) after metal-on-metal (MOM) artificial joint replacement. As such, a better understanding of the CoNPs-toxicity mechanism is necessary and urgent for the development of effective and safe detoxification drugs. Our purpose was to explore the role of bioactive nano-selenium (BNS, > 97%) in antagonizing the toxicity of CoNPs and its mechanism through the Keap1-Nrf2-ARE signaling pathway. To examine BNS detoxification, we exposed HUVEC cells to CoNPs and BNS for 24 h, before measuring cell activity, reactive oxygen species (ROS), the GSH level, inflammatory factors, and KNA signaling pathway-related transcript and protein expression. CoNPs stimulate intracellular inflammation and ROS production to bring about significant downregulation of cellular activity and the GSH level. Conversely, BNS reduces ROS generation and suppresses inflammatory factors within cells to reduce CoNPs-mediated cytotoxicity, possibly via the KNA signaling pathway. Based on our results, BNS antagonizes CoNPs toxic effects by suppressing ROS production through the KNA pathway. Our research provides new insight into the clinical treatment of CoNPs toxicity and explores the potential of BNS in detoxification therapy. Trial registration: no human participant.

Bioactive nano-selenium antagonizes cobalt nanoparticle- mediated oxidative stress via the Keap1-Nrf2-ARE signaling pathway

BackgroundAt present, no effective treatment exists for the clinical toxicity of cobalt nanoparticles (CoNPs) after metal-on-metal (MOM) artificial joint replacement. As such, a better understanding of the CoNPs-toxicity mechanism is necessary and urgent for the development of effective and safe detoxification drugs. Our purpose was to explore the role of bioactive nano-selenium (BNS) in antagonizing the toxicity of CoNPs and its mechanism through the Keap1-Nrf2-ARE signaling pathway. MethodsTo examine BNS detoxification, we exposed HUVEC cells to CoNPs (400μmol/l) and BNS (50μg/ml) for 24h, before measuring cell activity, reactive oxygen species (ROS), inflammatory factors, and KNA signaling pathway related transcript and protein expression. ResultsCoNPs stimulate intracellular inflammation and ROS production to bring about significant downregulation of cellular activity. Conversely, BNS reduces ROS generation and suppresses inflammatory factors within cells to reduce CoNPs-mediated cytotoxicity, possibly via the KNA signaling pathway. ConclusionsBased on our results, BNS antagonizes CoNPs toxic effects by suppressing ROS production through the KNA pathway. Our research provides new insight into the clinical treatment of CoNPs toxicity and explores the potential of BNS in detoxification therapy.

Free-Floating Aggregate and Single-Cell-Initiated Biofilms of Staphylococcus aureus

Periprosthetic joint infection (PJI) occurring after artificial joint replacement is a major clinical issue requiring multiple surgeries and antibiotic interventions. Staphylococcus aureus is the common bacteria responsible for PJI. Recent in vitro research has shown that staphylococcal strains rapidly form free-floating aggregates in the presence of synovial fluid (SF) with biofilm-like resistance to antimicrobial agents. However, the development of biofilms formed from these aggregates under shear have not been widely investigated. Thus, in this study, we examined the progression of attached biofilms from free-floating aggregates. Biofilms were grown for 24 h in flow cells on titanium discs after inoculation with either pre-aggregated or single planktonic cells. Image analysis showed no significant difference between the biofilm formed from aggregates vs. the planktonic cells in terms of biomass, surface area, and thickness. Regarding antibiotic susceptibility, there were 1 and 2 log reductions in biofilms formed from single cells and aggregates, respectively, when treated with vancomycin for 24 h. Thus, this study demonstrates the formation of biofilm from free-floating aggregates and follows a similar developmental time period and shows similar antibiotic tolerance to more traditionally inoculated in vitro flow cell biofilms.

Rheologic Behavior of Bovine Calf Serum

Recent studies have illuminated the rheological behavior of synovial fluid and the role of protein and hyaluronan (HA). However, with respect to artificial joint replacement in standardized wear simulations, bovine serum is used as fluid test medium. Little is known about the rheological characteristics of bovine serum, which are needed for precise tribological investigations. The steady shear viscosity η of bovine calf serum is determined for protein concentrations used in standardized wear simulations depending on shear rate γ˙ and temperature T. Additionally, the density of the serum is determined for both protein concentrations. The results show shear thinning behavior of bovine calf serum with a nearly Newtonian behavior in the range of high shear rates. Within the range of high shear rates, mean viscosities of η = 0.82–0.88 mPa·s were found for protein concentrations of 20 g/L and mean viscosities of η = 0.88–0.94 mPa·s for 30 g/L, decreasing with temperature. Densities of 1.004–1.005 g/cm3 and 1.007–1.008 g/cm3 were found for 20 and 30 g/L protein concentrations, respectively.

Treatment of Grade 3 and 4 Osteoarthritis with Intraoperatively Separated Adipose Tissue-Derived Stromal Vascular Fraction: A Comparative Case Series

Osteoarthritis (OA) is the most common form of arthritis of the joints. The stromal vascular fraction (SVF) is a regenerative cell population that can be isolated from adipose tissue. It is the immunomodulatory properties of the stromal vascular fraction that make it a promising candidate for the regenerative treatment of OA. Patients with grade 3 and 4 osteoarthritis were treated with the stromal vascular fraction with and without platelet-rich plasma (PRP) and followed up on their Knee Injury and Osteoarthritis Outcome Score (KOOS) score for 12 months, with MRI and subjective evaluation of the procedure. Magnetic resonance imaging (MRI) revealed a widening of the joint space, a restructuring of the cartilage, and an alleviation of effusions in the treated joints. In three of the four treatment groups, a substantial improvement of the KOOS scores was documented at the 12-month follow-up time point. According to the subjective evaluation, 67% of the patients were satisfied or very satisfied with the procedure and would recommend it to others. No serious adverse events or unwanted side effects related to the SVF treatment were observed or reported. Prior to an invasive artificial joint replacement, the treatment of arthritic knee joints with the intraarticular injection of autologous adipose tissue-derived SVF should be considered a regenerative treatment option.

QUANTITATIVE EVALUATION METHOD FOR TIBIOFIBULAR JOINT ALIGNMENT IN ANKLE OSTEOARTHRITIS BASED ON 3D BONE SIZE

Purpose: A remedy for ankle osteoarthritis is artificial joint replacement surgery. By estimating the relative positional difference (alignment) between the bone before and after deformation, precise artificial joint replacement surgery can be performed. By using the estimated alignment, an artificial ankle joint can ensure high satisfaction with less pain and can perform necessary functions. Although bone alignment is currently estimated from X-rays and computed tomography (CT) images, it is difficult to measure three-dimensional (3D) data from two-dimensional (2D) images. Although 3D data can be estimated using a 2D–3D registration method, it requires capturing the bone images multiple times and imposing considerable burden on the patient. In this paper, we propose a method to estimate the 3D bone alignment based on the size of the bone using principal component analysis (PCA), which requires scanning only one data. Method: In the proposed method, PCA is used to create a 3D bone model based on the bone thickness, and the bone alignment is estimated by the Go-ICP algorithm. In this study, the images of the foot were captured using a CT device, and the 3D bone model was created by stacking CT images. For improving the accuracy of the alignment, a reference model based on the bone thickness was created using PCA. Subsequently, the bone was overlapped and the alignment was estimated. Result: For the evaluation of the accuracy of alignment in the proposed method, three types of methods were used to create a bone model. The proposed method was found to be the most accurate with respect to the true value in five of the six evaluation criteria. In addition, the alignment of the tibiofibular joint was evaluated using the proposed method. Regarding the displacement in the [Formula: see text]-axis direction, there were significant differences in both Stage 3B and Stage 4 compared with the healthy subjects. In addition, the magnitude of rotation in the [Formula: see text]-axis direction showed a significant difference in stage 3B as compared with a healthy subject. Conclusion: Using the proposed method, we have shown that bone alignment can be estimated three-dimensionally by scanning the bone data once only. In addition, by comparing with the reference model using PCA based on the thickness of the bone, the accuracy of alignment is improved as compared with the reference model, which is not based on the bone thickness.

Staphylococcus aureus Aggregates on Orthopedic Materials under Varying Levels of Shear Stress

ABSTRACT Periprosthetic joint infection (PJI) occurring after artificial joint replacement is a major clinical issue requiring multiple surgeries and antibiotic interventions. Staphylococcus aureus is the bacterium most commonly responsible for PJI. Recent in vitro research has shown that staphylococcal strains rapidly form aggregates in the presence of synovial fluid (SF). We hypothesize that these aggregates provide early protection to bacteria entering the wound site, allowing them time to attach to the implant surface, leading to biofilm formation. Thus, understanding the attachment kinetics of these aggregates is critical in understanding their adhesion to various biomaterial surfaces. In this study, the number, size, and surface area coverage of aggregates as well as of single cells of S. aureus were quantified under various conditions on different orthopedic materials relevant to orthopedic surgery: stainless steel (316L), titanium (Ti), hydroxyapatite (HA), and polyethylene (PE). It was observed that, regardless of the material type, SF-induced aggregation resulted in reduced aggregate surface attachment and greater aggregate size than the single-cell populations under various shear stresses. Additionally, the surface area coverage of bacterial aggregates on PE was relatively high compared to that on other materials, which could potentially be due to the rougher surface of PE. Furthermore, increasing shear stress to 78 mPa decreased aggregate attachment to Ti and HA while increasing the aggregates’ average size. Therefore, this study demonstrates that SF induced inhibition of aggregate attachment to all materials, suggesting that biofilm formation is initiated by lodging of aggregates on the surface features of implants and host tissues. IMPORTANCE Periprosthetic joint infection occurring after artificial joint replacement is a major clinical issue that require repeated surgeries and antibiotic interventions. Unfortunately, 26% of patients die within 5 years of developing these infections. Staphylococcus aureus is the bacterium most commonly responsible for this problem and can form biofilms to provide protection from antibiotics as well as the immune system. Although biofilms are evident on the infected implants, it is unclear how these are attached to the surface in the first place. Recent in vitro investigations have shown that staphylococcal strains rapidly form aggregates in the presence of synovial fluid and provide protection to bacteria, thus allowing them time to attach to the implant surface, leading to biofilm formation. In this study, we investigated the attachment kinetics of Staphylococcus aureus aggregates on different orthopedic materials. The information presented in this article will be useful in surgical management and implant design.