Micro- and Nanomanufacturing for Biomedical Applications and Nanomedicine: A Perspective

Almost a century's dedicated research into micro- and nanomaterials has yielded fruitful development of preparation methods, achieving fine control over product properties among a broad spectrum of materials. One critical application of these materials lies within the healthcare sector for diagnostic, prophylactic, and therapeutic purposes. However, bench-to-bedside translations are still hindered by some unmet demands, especially the scaling-up from lab-scale preparation to industry-level production. The current review recapitulates the strategies of micro- and nanomaterial preparation from a holistic viewpoint. The similarities in synthesis and processing methods for various types of materials are highlighted. Furthermore, patents of commercialized nanomedicines are revisited to reveal a solid progress of micro- and nanomanufacturing in the last decade. In conclusion, further interdisciplinary research between fields in materials manufacturing is beneficial for the clinical translation and eventually unleashing the power of materials at small dimensions

Polymeric Nanocomposite Structures Based on Functionalized Graphene with Tunable Properties for Nervous Tissue Replacement

Electroconductive scaffolds can be a promising approach to repair conductive tissues when natural healing fails. Recently, nerve tissue engineering constructs have been widely investigated due to the challenges in creating a structure with optimized physiochemical and mechanical properties close to the native tissue. The goal of the current study was to fabricate graphene-containing polycaprolactone/gelatin/polypyrrole (PCL/gelatin/PPy) and polycaprolactone/polyglycerol-sebacate/polypyrrole (PCL/PGS/PPy) with intrinsic electrical properties through an electrospinning process. The effect of graphene on the properties of PCL/gelatin/PPy and PCL/PGS/PPy were investigated. Results demonstrated that graphene incorporation remarkably modulated the physical and mechanical properties of the scaffolds such that the electrical conductivity increased from 0.1 to 3.9 ± 0.3 S m–1 (from 0 to 3 wt % graphene) and toughness was found to be 76 MPa (PCL/gelatin/PPy 3 wt % graphene) and 143.4 MPa (PCL/PGS/PPy 3 wt % graphene). Also, the elastic moduli of the scaffolds with 0, 1, and 2 wt % graphene were reported as 210, 300, and 340 kPa in the PCL/gelatin/PPy system and 72, 85, and 92 kPa for the PCL/PGS/PPy system. A cell viability study demonstrated the noncytotoxic nature of the resultant scaffolds. The sum of the results presented in this study suggests that both PCL/gelatin/PPy/graphene and PCL/PGS/PPy/graphene compositions could be promising biomaterials for a range of conductive tissue replacement or regeneration applications

Grade Uncertainty and its Impact on Ore Grade Reconciliation between the Resource Model and the Mine

Major differences between estimated grade and actual grade are a usual problem in many open pit mines. The estimated grade is predicted in exploration stage from data obtained from boreholes, whereas the actual grade would be determined only after the mining operation. The poor reconciliation between the values of estimated and actual grades can cause major economic losses to the mining industry. Many different factors affect the reconciliation process in a mining operation. The nature of the orebody, the random uncertainty and the systematic errors are three main sources affecting the reconciliation process in exploration stage of the orebody. In this paper each source of uncertainty is studied and a probabilistic model is presented to determine the role of each item in total uncertainty of the grade parameter. The model ability was investigated in the study of real data taken from an iron open pit mine in Iran. The results showed the systematic uncertainty, the nature of the orebody and the random uncertainty are the main causes of poor reconciliation in the case study respectively

Magnetic Resonance Spectroscopy discriminates the response to microglial stimulation of wild type and Alzheimer's disease models.

Microglia activation has emerged as a potential key factor in the pathogenesis of Alzheimers disease. Metabolite levels assessed by magnetic resonance spectroscopy (MRS) are used as markers of neuroinflammation in neurodegenerative diseases, but how they relate to microglial activation in health and chronic disease is incompletely understood. Using MRS, we monitored the brain metabolic response to lipopolysaccharides (LPS)-induced microglia activation in vivo in a transgenic mouse model of Alzheimers disease (APP/PS1) and healthy controls (wild-type (WT) littermates) over 4 hours. We assessed reactive gliosis by immunohistochemistry and correlated metabolic and histological measures. In WT mice, LPS induced a microglial phenotype consistent with activation, associated with a sustained increase in macromolecule and lipid levels (ML9). This effect was not seen in APP/PS1 mice, where LPS did not lead to a microglial response measured by histology, but induced a late increase in the putative inflammation marker myoinositol (mI) and metabolic changes in total creatine and taurine previously reported to be associated with amyloid load. We argue that ML9 and mI distinguish the response of WT and APP/PS1 mice to immune mediators. Lipid and macromolecule levels may represent a biomarker of activation of healthy microglia, while mI may not be a glial marker

Norbornene chaotropic salts as low molecular mass ionic organogelators (LMIOGs)

Phenylalanine functionalised norbornene (9:Na) functions as a potent, low molecular-mass (MW = 333 Da) ionic organogelator with a minimum gelating concentration of 0.5 wt% in THF, i-PrOH, 1,4-dioxane and n-BuOH. Fibrous crystals form in the gel and X-ray crystallography identified a cation mediated helical assembly process controlled by the chirality of the phenylalanine. In additon to excellent gelating properties 9:Na readily forms aqueous biphasic and triphasic systems

Influence of gap size and development stages on the silvicultural characteristics of oriental beech (Fagus orientalis Lipsky) regeneration

We studied 11 gaps covered with beech saplings (< 1.30 m tall) in a reserve compartment (compartment 139, district one, Langa forest, watershed 36: Kazemrood) of the Caspian beech forest in N Iran. Two transects, each 2 m wide, were laid along the longest (N-S) and shortest (E-W) axis of each gap. Five micro sample plots, each 4 m2, were established: one at the center, and one at each corner. Qualitative and quantitative characteristics of saplings with a diameter at breast height less than 7.5 cm were examined in the micro sample plots. Analysis of variance (ANOVA) and Kruskal-Wallis test were performed using SPSS software for quantitative characteristics, and chi-square test for qualitative characteristics. Results indicated that medium-sized (200-500 m2) gaps promote the growth of oriental beech saplings of desirable silvicultural forms during decay and initial stages

The Increased Level of Serum p53 in Hepatitis B-Associated Liver Cirrhosis

BACKGROUND: The ability of tumour suppressor protein p53 (P53) to regulate cell cycle processes can be modulated by hepatitis B virus (HBV). While preliminary evidences indicates the involvement of protein-x of HBV (HBx) in altering p53 DNA binding, no further data have been accumulated for the significance of serum p53 in chronic hepatitis B virus infected patients. METHODS: 72 non-cirrhotic and 19 cirrhotic patients infected by HBV were enrolled for the analysis in this study. Enzyme linked immunosorbent assay (ELISA) was performed to study the concentrations of serum p53 protein. The tertiary structures of HBx and P53 were docked by Z-dock and Hex servers for in-silico protein-protein interaction analysis. RESULTS: There was a significant association between the serum p53 and cirrhosis (OR=1.81 95 CI: 1.017-3.2, P=0.044). Cirrhotic patients had higher level of serum p53 compare with chronic infection of HBV (1.98+/-1.22 vs. 1.29+/-0.72 U/ml, P=0.05). No evidence of correlation was seen between the different variables such as age, gender, log viral load, serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) with serum p53. Tertiary model shows that the amino acid residues from Arg110 to Lys132 of the N-terminal of P53 which is critical for ubiquitination, are bonded to a region in N- terminal of HBx amino acid residues from Arg19 to Ser33. CONCLUSION: There is an increase in serum p53 in HBV-related cirrhosis patients. In this case, HBx might be responsible for such higher concentration of p53 through HBx-p53 protein-protein interaction, as is shown by molecular modeling approach

Metal ion type significantly affects the morphology but not the activity of lipase-metal-phosphate nanoflowers

Enzyme&ndash;metal-ion&ndash;phosphate nanoflowers are high-surface area materials which are known to show higher activity than the constituting protein. Although the synthesis of hybrid nanoflowers has been demonstrated with a variety of proteins and reaction conditions, only di-valent metal ions have been tested to date. We expand on previous findings by testing a range of metal ions of different valence in co-presence with lipase from Burkholderia cepacia: Ag(I), Fe(II), Cu(II), Au(III). All metal ions produced colour precipitates, although the type of metal caused different precipitate morphologies under comparable reaction conditions: from nanoflowers to forests of nano-plates and crystal-like precipitates. In contrast, the type of metal ion did not appear to significantly affect the product\u27s specific enzyme activity, which remained greater than that of free lipase. This indicates that the type of metal ion and the macroscopic arrangement of the petals play a secondary role to that of the co-presence of the metal and phosphate ions in determining lipase nanoflower activity. The demonstrated ability to produce metal&ndash;phosphate-protein nanoflowers with a selection of different metals also opens the way to producing a wider range of functional, nanostructured, materials