Showing papers by "S. Thameem Dheen published in 2022"

A comparative investigation on the mechanical properties and cytotoxicity of Cubic, Octet, and TPMS gyroid structures fabricated by selective laser melting of stainless steel 316L.

Abstract: Metallic lattice structures can be fabricated by selective laser melting (SLM) with purposefully designed pores and controlled pore sizes that can bio mimic the natural bone, providing adequate mechanical and biological support for the patients. Strut-based structures, like Cubic, Octet; and sheet-based structures, like triply periodic minimal surface (TPMS) gyroid, have been studied extensively in the past. However, it lacks enough comparative study on the mechanical properties and cytotoxicity among these structures. Therefore, Cubic, Octet, and TPMS gyroid of Stainless steel 316 L (SS316L) are designed, manufactured, and characterized at 40/50/60% relative densities in this study. Moreover, the flowability, density characteristics, and cytotoxicity of SS316L powder are validated to ascertain its suitability for 3D printing and implant application. Based on refining the Gibson-Ashby model, it is possible to predict or design the mechanical properties via adjusting the relative densities. The results indicate these structures demonstrated appropriate Young's modulus and outstanding biocompatibility.

A biomechanical evaluation on Cubic, Octet, and TPMS gyroid Ti6Al4V lattice structures fabricated by selective laser melting and the effects of their debris on human osteoblast-like cells.

Abstract: Lattice structures are widely used in orthopedic implants due to their unique features, such as high strength-to-weight ratios and adjustable biomechanical properties. Based on the type of unit cell geometry, lattice structures may be classified into two types: strut-based structures and sheet-based structures. In this study, strut-based structures (Cubic & Octet) and sheet-based structure (triply periodic minimal surface (TPMS) gyroid) were investigated. The biomechanical properties of the three different Ti6Al4V lattice structures fabricated by selective laser melting (SLM) were investigated using room temperature compression testing. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) were used to check the 3D printing quality with regards to defects and quantitative compositional information of 3D printed parts. Experimental results indicated that TPMS gyroid has superior biomechanical properties when compared to Cubic and Octet. Also, TPMS gyroid was found to be less affected by the variations in relative density. The biocompatibility of Ti6Al4V lattice structures was validated through the cytotoxicity test with human osteoblast-like SAOS2 cells. The debris generated during the degradation process in the form of particles and ions is among the primary causes of implant failure over time. In this study, Ti6Al4V particles with spherical and irregular shapes having average particle sizes of 36.5 μm and 28.8 μm, respectively, were used to mimic the actual Ti6Al4V particles to understand their harmful effects better. Also, the effects and amount of Ti6Al4V ions released after immersion within the cell culture media were investigated using the indirect cytotoxicity test and ion release test.

Nutrient sensitive protein O-GlcNAcylation modulates the transcriptome through epigenetic mechanisms during embryonic neurogenesis

Abstract: Maternal hyperglycemia and elevated O-GlcNAc levels perturb promoter bivalency and lead to transcriptional up-regulation of neurogenic transcription factors during embryonic neurogenesis. Protein O-GlcNAcylation is a dynamic, nutrient-sensitive mono-glycosylation deposited on numerous nucleo-cytoplasmic and mitochondrial proteins, including transcription factors, epigenetic regulators, and histones. However, the role of protein O-GlcNAcylation on epigenome regulation in response to nutrient perturbations during development is not well understood. Herein we recapitulated early human embryonic neurogenesis in cell culture and found that pharmacological up-regulation of O-GlcNAc levels during human embryonic stem cells’ neuronal differentiation leads to up-regulation of key neurogenic transcription factor genes. This transcriptional de-repression is associated with reduced H3K27me3 and increased H3K4me3 levels on the promoters of these genes, perturbing promoter bivalency possibly through increased EZH2-Thr311 phosphorylation. Elevated O-GlcNAc levels also lead to increased Pol II-Ser5 phosphorylation and affect H2BS112O-GlcNAc and H2BK120Ub1 on promoters. Using an in vivo rat model of maternal hyperglycemia, we show similarly elevated O-GlcNAc levels and epigenetic dysregulations in the developing embryo brains because of hyperglycemia, whereas pharmacological inhibition of O-GlcNAc transferase (OGT) restored these molecular changes. Together, our results demonstrate O-GlcNAc mediated sensitivity of chromatin to nutrient status, and indicate how metabolic perturbations could affect gene expression during neurodevelopment.

The effects of various processing parameters on the mechanical properties and biocompatibility of Fe-based bulk metallic glass processed by selective laser melting at the constant energy density

Abstract: • As compared to 316 L SS, Fe-based BMG exhibits optimal mechanical properties, adequate corrosion resistance, and excellent biocompatibility. • regardless of the various processing parameters, nearly fully amorphous structures specimen can be produced by SLM. • At the same energy density, the hardness and elastic modulus can be varied by adjusting laser power and scanning speed. • Lower processing parameters (at the same energy) can generate Fe-based BMG with a rougher surface, which can release more beneficial ions for better biocompatibility. The unique properties of bulk metallic glass (BMG) render it an excellent material for bone-implant applications. BMG samples are difficult to produce directly because of the critical cooling rate of molding. Advancements in additive manufacturing technologies, such as selective laser melting (SLM), have enabled the development of BMG. The successful production of materials via SLM relies significantly on the processing parameters; meanwhile, the overall energy density affects the crystallization and, thus, the final properties. Therefore, to further determine the effects of the processing parameters, SLM is performed in this study to print Fe-based BMG with different properties three dimensionally using selected processing parameters but a constant energy density. The printed amorphous Fe-based BMG outperforms the typical 316 L stainless steel (316 L SS) in terms of mechanical properties and corrosion resistance. Moreover, observations from nanoindentation tests indicate that the hardness and elastic modulus of the Fe-based BMG can be customized explicitly by adjusting the SLM processing parameters. Indirect cytotoxicity results show that the Fe-based BMG can enhance the viability of SAOS2 cells, as compared with 316 L SS. These intriguing results show that Fe-based BMG should be investigated further for orthopedic implant applications.

Biocompatibility and Mechanical Properties Evaluation of Ti-6Al-4V Lattice Structures with Varying Porosities

Abstract: Ti-6Al-4V is one of the popular choices for biomedical implants due to multiple advantages, such as corrosion resistance, high strength-to-weight ratio, biocompatibility, lightweight, durability, and osseointegration properties. However, Young’s modulus (E) of Ti-6Al-4V is much higher than the E of natural human bone, which may lead to stress shielding. Therefore, it is critical that we need to fabricate the implant with specific mechanical properties that can match the patient’s existing bone. With the advent of 3D printing, we now can design porous structures with the most suitable E through adjusting porosity to suit individual needs. Porous structures with various porosities were manufactured by selective laser melting (SLM). Mechanical testing was performed to show that the E of the printed samples was related to the porosities only. Based on the simulated and actual results, there are still many areas that can be improved to enhance the quality of the printed structures. Indirect cytotoxicity tests were performed to verify the biocompatibility of the porous structures.

Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus

Abstract: Objective: To investigate microRNA (miRNA) expression profiles before and after pilocarpine-induced status epilepticus (SE) in the cornu ammonis (CA) and dentated gyrus (DG) areas of the mouse hippocampus, and to predict the downstream proteins and related pathways based on bioinformatic analysis. Methods: An epileptic mouse model was established using a pilocarpine injection. Brain tissues from the CA and DG were collected separately for miRNA analysis. The miRNAs were extracted using a kit, and the expression profiles were generated using the SurePrint G3 Mouse miRNA microarray and validated. The intersecting genes of TargetScan and miRanda were selected to predict the target genes of each miRNA. For gene ontology (GO) studies, the parent-child-intersection (pci) method was used for enrichment analysis, and Benjamini-Hochberg was used for multiple test correction. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to detect disease-related pathways among the large list of miRNA-targeted genes. All analyses mentioned above were performed at the time points of control, days 3, 14, and 60 post-SE. Results: Control versus days 3, 14, and 60 post-SE: in the CA area, a total of 131 miRNAs were differentially expressed; 53, 49, and 26 miRNAs were upregulated and 54, 10, and 22 were downregulated, respectively. In the DG area, a total of 171 miRNAs were differentially expressed; furthermore, 36, 32, and 28 miRNAs were upregulated and 78, 58, and 44 were downregulated, respectively. Of these, 92 changed in both the CA and DG, 39 only in the CA, and 79 only in the DG area. The differentially expressed miRNAs target 11–1630 genes. Most of these proteins have multiple functions in epileptogenesis. There were 15 common pathways related to altered miRNAs: nine different pathways in the CA and seven in the DG area. Conclusions: Stage- and subfield-associated hippocampal miRNA expression patterns are closely related to epileptogenesis, although the detailed mechanisms need to be explored in the future.