Why Is Tantalum Less Susceptible to Bacterial Infection?

Periprosthetic infection is one of the trickiest clinical problems, which often leads to disastrous consequences. The emergence of tantalum and its derivatives provides novel ideas and effective methods to solve this problem and has attracted great attention. However, tantalum was reported to have different anti-infective effects in vivo and in vitro, and the inherent antibacterial capability of tantalum is still controversial, which may restrict its development as an antibacterial material to some extent. In this study, the polished tantalum was selected as the experimental object, the implant-related tibia osteomyelitis model was first established to observe whether it has an anti-infective effect in vivo compared to titanium, and the early studies found that the tantalum had a lower infectious state in the implant-related tibia osteomyelitis model in vivo than titanium. However, further in vitro studies found that the polished tantalum was not superior to the titanium against bacterial adhesion and antibacterial efficacy. In addition, we focus on the state of interaction between cells, bacteria and materials to restore the internal environment as realistically as possible. We found that the adhesion of fibroblasts to tantalum was faster and better than that of titanium. Moreover, what is more, interesting is that, in the early period, bacteria were more likely to adhere to cells that had already attached to the surface of tantalum than to the bare surface of it, and over time, the cells eventually fell off the biomaterials and took away more bacteria in tantalum, making it possible for tantalum to reduce the probability of infection in the body through this mechanism. Moreover, these results also explained the phenomenon of the "race for the surface" from a completely different perspective. This study provides a new idea for further exploring the relationship between bacteria and host tissue cells on the implant surface and a meaningful clue for optimizing the preparation of antibacterial implants in the future.

m6A-Related lncRNAs Predict Overall Survival of Patients and Regulate the Tumor Immune Microenvironment in Osteosarcoma.

Background: m6A-related lncRNAs have demonstrated great potential tumor diagnostic and therapeutic targets. The goal of this work was to find m6A-regulated lncRNAs in osteosarcoma patients. Method: The Cancer Genome Atlas (TCGA) database was used to retrieve RNA sequencing and medical information from osteosarcoma sufferers. The Pearson's correlation test was used to identify the m6A-related lncRNAs. A risk model was built using univariate and multivariable Cox regression analysis. Kaplan-Meier survival analysis and receiver functional requirements were used to assess the risk model's performance (ROC). By using the CIBERSORT method, the associations between the relative risks and different immune cell infiltration were investigated. Lastly, the bioactivities of high-risk and low-risk subgroups were investigated using Gene Set Enrichment Analysis (GSEA). Result: A total of 531 m6A-related lncRNAs were obtained from TCGA. Seven lncRNAs have demonstrated prognostic values. A total of 88 OS patients were separated into cluster 1, cluster 2, and cluster 3. The overall survival rate of OS patients in cluster 3 was more favorable than that of those in cluster 1 and cluster 2. The average Stromal score was much higher in cluster 1 than in cluster 2 and cluster 3 (P < 0.05). The expression levels of lncRNAs used in the construction of the risk prediction model in the high-risk group were generally lower than those in the low-risk group. Analysis of patient survival indicated that the survival of the low-risk group was higher than that of the high-risk group (P < 0.0001) and the area under the curve (AUC) of the ROC curve was 0.719. Using the CIBERSORT algorithm, the results revealed that Macrophages M0, Macrophages M2, and T cells CD4 memory resting accounted for a large proportion of immune cell infiltration. By GSEA analysis, our results implied that the high-risk group was mainly involved in unfolded protein response, DNA repair signaling, and epithelial-mesenchymal transition signaling pathway and glycolysis pathway; meanwhile, the low-risk group was mainly involved in estrogen response early and KRAS signaling pathway. Conclusion: Our investigation showed that m6A-related lncRNAs remained tightly connected to the immunological microenvironment of osteosarcoma tumors, potentially influencing carcinogenesis and development. The immune microenvironment and immune-related biochemical pathways can be changed by regulating the transcription of M6A modulators or lncRNAs. In addition, we looked for risk-related signaling of m6A-related lncRNAs in osteosarcomas and built and validated the risk prediction system. The findings of our current analysis will facilitate the assessment of outcomes and the development of immunotherapies for sufferers of osteosarcomas.

A composite scaffold of Wharton's jelly and chondroitin sulphate loaded with human umbilical cord mesenchymal stem cells repairs articular cartilage defects in rat knee.

To evaluate the performance of a composite scaffold of Wharton's jelly (WJ) and chondroitin sulfate (CS) and the effect of the composite scaffold loaded with human umbilical cord mesenchymal stem cells (hUCMSCs) in repairing articular cartilage defects, two experiments were carried out. The in vitro experiments involved identification of the hUCMSCs, construction of the biomimetic composite scaffolds by the physical and chemical crosslinking of WJ and CS, and testing of the biomechanical properties of both the composite scaffold and the WJ scaffold. In the in vivo experiments, composite scaffolds loaded with hUCMSCs and WJ scaffolds loaded with hUCMSCs were applied to repair articular cartilage defects in the rat knee. Moreover, their repair effects were evaluated by the unaided eye, histological observations, and the immunogenicity of scaffolds and hUCMSCs. We found that in vitro, the Young's modulus of the composite scaffold (WJ-CS) was higher than that of the WJ scaffold. In vivo, the composite scaffold loaded with hUCMSCs repaired rat cartilage defects better than did the WJ scaffold loaded with hUCMSCs. Both the scaffold and hUCMSCs showed low immunogenicity. These results demonstrate that the in vitro construction of a human-derived WJ-CS composite scaffold enhances the biomechanical properties of WJ and that the repair of knee cartilage defects in rats is better with the composite scaffold than with the single WJ scaffold if the scaffold is loaded with hUCMSCs.

A novel elastic and controlled-release poly(ether-ester-urethane)urea scaffold for cartilage regeneration.

In the tissue engineering of cartilage, scaffolds with appropriate elasticity and controlled-release properties are essential. Herein, we synthesized a poly(ether-ester-urethane)urea scaffold with a pendant amino group (PEEUUN) through a de-protection process from PEEUU-Boc polymers and grafted kartogenin (KGN) onto the PEEUUN scaffolds (PEEUUN-KGN). Characterization, performance tests, scaffold biocompatibility analysis, and chondrogenesis evaluation both in vitro and in vivo were conducted. The results revealed that the PEEUUN-KGN scaffolds were degradable and three-dimensional (3D) with interconnected pores, and possessed good elasticity, as well as excellent cytocompatibility. Meanwhile, KGN on the PEEUUN-KGN scaffolds underwent stable sustained release for a long time and promoted human umbilical cord mesenchymal stem cells (HUCMSCs) to differentiate into chondrocytes in vitro, thus enhancing cartilage regeneration in vivo. In conclusion, the present PEEUUN-KGN scaffolds would have application potential for cartilage tissue engineering.

Storage solution containing hydrogen improves the preservation effect of osteochondral allograft.

As an ideal antioxidant and anti-apoptotic substance, hydrogen (H2) has protective effects on many isolated organs, such as the heart, lung and kidney. In this study, we explore whether H2 improves the preservation effect of osteochondral allograft by adding it to Dulbecco's Modified Eagle Medium (DMEM) solution during the tissue culture stage. The osteochondral allograft apparatus was used to harvest 60 pieces of cylindrical allografts (l = 10 mm, d = 6 mm) cartilage in the lateral loading area of the femoral condyle from the pig knee joint in the aseptic condition, and the grafts were randomly divided into 4 groups: Control group (DMEM solution without hydrogen); H-1 group (DMEM solution with hydrogen concentration of 0.2 mmol/L); H-2 group (DMEM solution with hydrogen concentration of 0.4 mmol/L); and H-3 group (DMEM solution with hydrogen concentration of 0.8 mmol/L). The chondrocyte viability, histological changes (hematoxylin and eosin staining, Safranine O staining, and collagen type II immunohistochemistry staining) and biomechanical properties (Young's modulus) of the osteochondral allograft were investigated after 28 days' storage. The chondrocyte viability and proteoglycan and collagen type II contents in the H-3 and H-2 groups were higher than that in the Control and H-1 groups, and the H-3 group had the highest values. However, significant differences were not observed between the four groups based on Young's modulus. Hydrogen as an additive to the DMEM solution improved the preservation effect of osteochondral allograft. The preservation effect of hydrogen occurred in a concentration-dependent manner.