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During binderjetting of bioceramics, many commercial 3D printers dispense binder in a default 'core-shell' manner. Using such a conventional approach, more binder is dispensed at the periphery (shell) and less binder at the 'core' of the structure. The inhomogeneous binding of the powder particles from the shell to the core significantly impacts the microstructure and biomechanical properties. To address this, we hypothesised 'segmentation' of a 3D printable design file by slicing and discretising with an array of thin solid "segments", separated with an infinitesimal gap in a periodic manner. In this novel approach, the printing software commands the printhead to print each of the "segments" individually. The inter-segment and intra-segment binder "bleeding" among the segments results in a printed part with a homogeneously bound cross-section, without any "core-shell" effect. This hypothesis was experimentally validated by better microstructure, improved density, and enhanced mechanical strength properties in binderjet printed 3 mol% yttria stabilised ZrO 2. [ABSTRACT FROM AUTHOR]

The coastal and low-lying areas of the Indian Sundarban are highly vulnerable to multiple hazards. Cyclonic hazards and floods have become a regular phenomenon in this fragile region. The villages and their households of this region are very much vulnerable to embankment breaching. Embankments in this region have been built since 1770, but it was so much unsuccessful in coping with storm surges or flood hazards. The study focuses on assessing the vulnerability of households that are spatially affected by embankment breaching. The methodology is composed of four dimensions of vulnerability including social, economic, physical, and environmental, which cover thirty-four indicators. From dimension-wise vulnerability, the overall vulnerability of households has been estimated. Based on the proximity to the embankment breaching location and impact, 330 households from eleven villages were selected to conduct the household survey. The study also adopted the relative effect score method to delineate the influence of indicators on the vulnerability of each specific village. The result shows that households belonging to Patibunia, Lakshmipur Abad, and Ganeshnagar occupy a very high categorical position in overall household vulnerability. The higher degree of exposure due to embankment breaching, unequal infrastructure, unstable economic structure, and a low level of education is considered to be highly sensitive towards vulnerability. The method is flexible and can be replicated and modified in other spatial scales for rapid decision-making. [Display omitted] • Vulnerability at the household level has been assessed using the Vulnerability Index of individual households. • Each household with its specific ID can distinguish the level of vulnerability. • A large number of households fall under the moderate to high vulnerable category. • Easily demarcate the vulnerable households and can access emergency response. [ABSTRACT FROM AUTHOR]

Examples of units with two performance characteristics that degrade over time are ubiquitous in reliability engineering. In this article, we develop a flexible model for bivariate degradation data pertaining to units in which the degradation processes corresponding to the performance characteristics are likely dependent on each other. The proposed model has two features: the degradation processes are marginally modelled by gamma processes, and the dependence between them is modelled by a shared frailty term that is assumed to follow the generalized gamma distribution. We show that this model is far more flexible and efficient than many of the commonly used models for capturing dependence between the performance characteristics. A computational technique for the maximum likelihood estimation, based on Monte Carlo simulation, is developed for the proposed model. Then, the method of estimation is evaluated through an elaborate Monte Carlo simulation study. The joint reliability function of the unit with two performance characteristics and its estimation are also discussed in this general setting. The proposed model is extended to the case of multiple performance characteristics. Finally, a case study is presented in which a real degradation data pertaining to fatigue cracks is analysed through the proposed model to demonstrate its usefulness. • A flexible model for bivariate degradation data involving gamma processes. • The dependence is captured by a frailty effect following generalized gamma model. • Likelihood inference based on Monte Carlo method; efficient and easy-to-use. • Reliability function of units with two performance characteristics is developed. • Application on fatigue crack data; proposed model provides adequate fit. [ABSTRACT FROM AUTHOR]

• 3D binderjet printing based design and fabrication of patient specific acrylic flap for cranioplasty is safe and restores cosmesis accurately as determined by Cranial index of symmetry. • Clinically acceptable structural and mechanical properties of the PMMA implant could be obtained with our design protocol. • The use of 3D binderjet printer and conventional casting of PMMA flap allows an affordable option for cranioplasty in a resource constrained setting. There exists a significant demand to develop patient-specific prosthesis in reconstruction of cranial vaults after decompressive craniectomy. we report here, the outcomes of an unicentric pilot study on acrylic cranial prosthesis fabricated using a 3D printed cranium model with its clinically relevant mechanical properties. The semi-crystalline polymethyl methacrylate (PMMA) implants, shaped to the cranial defects of 3D printed cranium model, were implanted in 10 patients (mean age, 40.8 ± 14.8 years). A binderjet 3D printer was used to create patient-specific mould and PMMA was casted to fabricate prosthesis which was analyzed for microstructure and properties. Patients were followed up for allergy, infection and cosmesis for a period of 6 months. As-cast PMMA flap exhibited hardness of 15.8 ± 0.24Hv, tensile strength of 30.7 ± 3.9 MPa and elastic modulus of 1.5 ± 0.1 GPa. 3D microstructure of the semi-crystalline acrylic implant revealed 2.5–15 µm spherical isolated pores. The mean area of the calvarial defect in craniectomy patients was 94.7 ± 17.4 cm2. We achieved a cranial index of symmetry (CIS -%) of 94.5 ± 3.9, while the average post-operative Glasgow outcome scale (GOS) score recorded was 4.2 ± 0.9. 3D printing based patient-specific design and fabrication of acrylic cranioplasty implant is safe and achieves acceptable cosmetic and clinical outcomes in patients with decompressive craniectomy. Our study ensured clinically acceptable structural and mechanical properties of implanted PMMA, suggesting that a low cost 3D printer based PMMA flap is an affordable option for cranioplasty in resource constrained settings. [ABSTRACT FROM AUTHOR]

Stem cell research is one of the most promising and fascinating field in regenerative medicine and dentistry. The use of embryonic stem cells is restricted due to the very many ethical issues while the dental pulp stem cell research is relatively free from such embargoes. Recently published research articles relating to dental pulp stem cells are voluminous but are very diversifying in nature. The observations of these researchers require critical analysis and evaluation in a focused way as is presented in this review article. [ABSTRACT FROM AUTHOR]

Although rapamycin is a very effective drug for rodents with polycystic kidney disease (PKD), it is not encouraging in the clinical trials due to the suboptimal dosages compelled by the off-target side effects. We here report the generation, characterization, specificity, functionality, pharmacokinetic, pharmacodynamic and toxicology profiles of novel polycystic kidney-specific-targeting nanoparticles (NPs). We formulated folate-conjugated PLGA-PEG NPs, which can be loaded with multiple drugs, including rapamycin (an mTOR inhibitor) and antioxidant 4-hydroxy-TEMPO (a nephroprotective agent). The NPs increased the efficacy, potency and tolerability of rapamycin resulting in an increased survival rate and improved kidney function by decreasing side effects and reducing biodistribution to other organs in PKD mice. The daily administration of rapamycin-alone (1 mg/kg/day) could now be achieved with a weekly injection of NPs containing rapamycin (379 μg/kg/week). This polycystic kidney-targeting nanotechnology, for the first time, integrated advances in the use of 1) nanoparticles as a delivery cargo, 2) folate for targeting, 3) near-infrared Cy5-fluorophore for in vitro and in vivo live imaging, 4) rapamycin as a pharmacological therapy, and 5) TEMPO as a combinational therapy. The slow sustained-release of rapamycin by polycystic kidney-targeting NPs demonstrates a new era of nanomedicine in treatment for chronic kidney diseases at clinically relevant doses. [Display omitted] [ABSTRACT FROM AUTHOR]

Improvement of cell migration by the nano-topographical modification of implant surface can directly or indirectly accelerate wound healing and osseointegration between bone and implant. Therefore, modification of the implant surface was done with TiO 2 nanorod (NR) arrays to develop a more osseointegration-friendly implant in this study. Modulating the migration of a cell, adhered to a scaffold, by the variations of NR diameter, density and tip diameter in vitro is the primary objective of the study. The fluid structure interaction method was used, followed by the submodelling technique in this multiscale analysis. After completing a simulation over a global model, fluid structure interaction data was applied to the sub-scaffold finite element model to predict the mechanical response over cells at the cell-substrate interface. Special focus was given to strain energy density at the cell interface as a response parameter due to its direct correlation with the migration of an adherent cell. The results showed a huge rise in strain energy density after the addition of NRs on the scaffold surface. It also highlighted that variation in NR density plays a more effective role than the variation in NR diameter to control cell migration over a substrate. However, the effect of NR diameter becomes insignificant when the NR tip was considered. The findings of this study could be used to determine the best nanostructure parameters for better osseointegration. [Display omitted] • The surface of a Ti 6 Al 4 V scaffold was modified with TiO 2 nanorods (NRs). • The effect on cell migration due to different NRs features was evaluated through multiscale modelling. • Strain energy density was considered as a response parameter for cell migration. • The presence of NRs on the scaffold surface significantly enhances cell migration. • The influence of NR density on cell migration is more than NR diameter. [ABSTRACT FROM AUTHOR]

An increasing demand for directed assembly of biomaterials has inspired the development of bioprinting, which facilitates the assembling of both cellular and acellular inks into well-arranged three-dimensional (3D) structures for tissue fabrication. Although great advances have been achieved in the recent decade, there still exist issues to be addressed. Herein, a review has been systematically performed to discuss the considerations in the entire procedure of bioprinting. Though bioprinting is advancing at a rapid pace, it is seen that the whole process of obtaining tissue constructs from this technique involves multiple-stages, cutting across various technology domains. These stages can be divided into three broad categories: pre-bioprinting, bioprinting and post-bioprinting. Each stage can influence others and has a bearing on the performance of fabricated constructs. For example, in pre-bioprinting, tissue biopsy and cell expansion techniques are essential to ensure a large number of cells are available for mass organ production. Similarly, medical imaging is needed to provide high resolution designs, which can be faithfully bioprinted. In the bioprinting stage, compatibility of biomaterials is needed to be matched with solidification kinetics to ensure constructs with high cell viability and fidelity are obtained. On the other hand, there is a need to develop bioprinters, which have high degrees of freedom of movement, perform without failure concerns for several hours and are compact, and affordable. Finally, maturation of bioprinted cells are governed by conditions provided during the post-bioprinting process. This review, for the first time, puts all the bioprinting stages in perspective of the whole process of bioprinting, and analyzes their current state-of-the art. It is concluded that bioprinting community will recognize the relative importance and optimize the parameter of each stage to obtain the desired outcomes. [ABSTRACT FROM AUTHOR]

Metabolic alterations of oral epithelial cells under oxidative stress are important signatures for early diagnosis of oral cancer. Amongst different metabolic alterations, non-invasive photo-diagnostic methods have been extensively used for determining cellular heme metabolism and accumulation of protoporphyrin IX (PpIX) under administration of suitable photosensitizer. In this study, we report these metabolic alterations by direct analysis of oral exfoliated cells obtained from individuals with prolonged smoking habit without the exogenous administration of any photosensitizer. The relative expression level of relevant biomolecules of study groups were compared with clinically diagnosed and histopathologically confirmed leukoplakia (OLPK) and oral squamous cell carcinoma (OSCC) patients. The energy imbalance and variation in ‘redox ratio’ were examined through spectroscopic studies which showed an increasing trend (p < 0.001) in smokers to OSCC groups in comparison to nonsmoker control. Gene expression of important intermediates of the heme metabolic pathway ( viz . 5-aminolevulinate synthase 1 (ALAS1), Ferrochelatase (FECH), hemeoxygenase 1 (HO-1) and ATP binding cassette subfamily G member 2 (ABCG2)) which affect production of PpIX was assessed. Relative mRNA level of ALAS1 and HO1 was upregulated whereas mRNA level of other genes ( viz . FECH and ABCG2) were found to be downregulated in smokers as well as in cancer groups. Outcome of different spectroscopic studies on exfoliated cells ( viz . fluorescence, atomic absorption and Fourier transform infrared spectroscopy) corroborated with the expression of biomarkers related to cellular endogenous metabolism related to heme cycle. This study indicates significant alterations in endogenous metabolic products, and cellular functional groups in oral epithelial cells among the study groups. Our study reports a strong possibility of diagnosis of early cancer signatures amongst habitual smokers by direct and non-invasive assessment of metabolic status of oral epithelial cells without exogenous administration of photosensitizers. The knowledge accrued from the study may guide clinicians in precise detection of precancer trend in the susceptible population through a noninvasive rapid screening method. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal/stem cells (MSCs) are multipotent cells that offer a promising outcome in the field of regenerative medicine. MSCs are present in various tissues including bone marrow, fat, skin, and placenta. The interest in clinical application of these mesoderm-derived MSCs is primarily fueled by their high self-renewal capacity and multipotency. Although, early studies indicated limited differentiation capacity of MSCs into same cell lineages from which they were isolated, subsequent investigations showed differentiation potential into other cell types of mesoderm origin including osteoblasts, adipocytes, fibroblasts, cardiomyocytes, and chondrocytes. Furthermore, MSCs exhibit a remarkable feature of transdifferentiation into ectodermal, neuroectodermal, and endodermal cells, phenomena referred to as ‘stem cell plasticity’. This opened the possibility of clinical applications of MSCs in the regeneration of other tissues like corneal reconstruction, treatment of acute lung injury, oral mucosal regeneration, homing of MSCs for regeneration at sites of injury etc. Though several evidence have accrued demonstrating this phenomenon, there is still a gap in understanding the molecular mechanism of such transitions which will be important to efficiently control the process. Interestingly, the process can be drawn a parallel with the Mesenchymal to Epithelial Transitions (MET) that takes place inside the body during embryonic development or certain pathophysiological conditions. In this review, a brief attempt is first made to understand the evidence of MSC transdifferentiation based on the current knowledge about MET. We then specifically focus on systematic presentation and analysis of the microenvironment factors involved in MSC transdifferentiation to epithelial lineages which would have applications in regenerative medicine. [ABSTRACT FROM AUTHOR]

Habitual smokers are known to be at higher risk for developing oral cancer, which is increasing at an alarming rate globally. Conventionally, oral cancer is associated with high mortality rates, although recent reports show the improved survival outcomes by early diagnosis of disease. An effective prediction system which will enable to identify the probability of cancer development amongst the habitual smokers, is thus expected to benefit sizable number of populations. Present work describes a non-invasive, integrated method for early detection of cellular abnormalities based on analysis of different cyto-morphological features of exfoliative oral epithelial cells. Differential interference contrast (DIC) microscopy provides a potential optical tool as this mode provides a pseudo three dimensional (3-D) image with detailed morphological and textural features obtained from noninvasive, label free epithelial cells. For segmentation of DIC images, gradient vector flow snake model active contour process has been adopted. To evaluate cellular abnormalities amongst habitual smokers, the selected morphological and textural features of epithelial cells are compared with the non-smoker (−ve control group) group and clinically diagnosed pre-cancer patients (+ve control group) using support vector machine (SVM) classifier. Accuracy of the developed SVM based classification has been found to be 86% with 80% sensitivity and 89% specificity in classifying the features from the volunteers having smoking habit. [ABSTRACT FROM AUTHOR]

Two different silica based (MSU-2 and MCM-41) curcumin loaded mesoporous materials V3 and V6 were synthesized and characterized by several physico-chemical techniques. Release kinetic study revealed the slow and sustained release of curcumin from those materials in blood simulated fluid (pH: 7.4). The materials V3 and V6 were found to be biocompatible in non-cancerous CHO cell line while exhibiting significant cytotoxicity in different cancer cells (human lung carcinoma cells: A549, human breast cancer cells: MCF-7, mouse melanoma cells: B16F10) compared to pristine curcumin indicating the efficacy of the mesoporous silica materials based drug delivery systems (DDSs). The generation of intracellular reactive oxygen species (ROS) and down regulation of anti-apoptotic protein leading to the induction of apoptosis were found to be the plausible mechanisms behind the anti-cancer activity of these DDSs. These results suggest that curcumin-loaded drug delivery system may be successfully employed as an alternative treatment strategy for cancer therapeutics through a nanomedicine approach in near future. [ABSTRACT FROM AUTHOR]

Docetaxel (DTX) is an anticancer drug that is used alone and in combination with other drugs to treat tumours. However, it suffers from the drawback of non-specific cytotoxicity. To improve the therapeutic potential of DTX, we report the synthesis of cRGDfK peptide-conjugated succinoyl-TPGS (tocopheryl polyethylene glycol succinate) nanomicelles for targeted delivery of DTX. Among RGD (Arg-Gly-Asp) peptides, cRGDfK peptide shows specificity towards α v β 3 integrin receptors that are most commonly over-expressed in tumour cells. To cRGDfK peptide, succinoylated TPGS was synthesised and conjugated to cRGDfK peptide using a carbodiimide reaction. Peptide-conjugated DTX loaded nanomicelles (PDNM) displayed small particle size with a narrow distribution, controlled drug release and high physicochemical stability. Cytotoxicity, cellular uptake, apoptosis and anti-angiogenic comparisons of unconjugated nanomicelles to PDNM in DU145 human prostate cancer cells and HUVECs (Human Umblical Vein Endothelial Cells) clearly revealed the importance of the cRGDfK peptide in enhancing the drug delivery performance of nanomicelles. From the Clinical Editor Common to many chemotherapeutic agents for cancer, systemic toxicity remains a big concern. In this article, the authors attempted to address this issue by conjugating RGD based peptides to Docetaxel, which would target integrins expressed on tumor cell surface. The experimental data revealed enhanced drug delivery. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin, because of its distinguishing ability to inhibit activation of transcription factor linked to chemoresistance and drug transporters, is now being co-administered with various potent anti-cancer drugs. In the present study, we report on such potentiating capabilities of curcumin in anti-angiogenic cancer therapy. With a view to simultaneously deliver curcumin and doxorubicin to tumor vasculature in anti-angiogenic cancer therapy, herein we report on the design & synthesis of a tumor vasculature targeting pegylated RGDK-lipopeptide. We show that curcumin & doxorubicin co-encapsulated within the liposomes of the presently described pegylated RGDK-lipopeptide exhibit synergism in inhibiting proliferation, invasion and migration of both tumor and endothelial cells presumably by inhibiting proliferation and metastasis related genes both at mRNA & protein levels. Pronounced tumor growth inhibition was observed in mice treated with formulations containing both the drugs. Tumor growth inhibition was found to be 2–3 folds less in mice treated with formulations containing only curcumin or only doxorubicin. The presently described liposomal system is expected to find future use for simultaneously delivering potentially any combinations of hydrophilic and hydrophobic potent small molecule cancer therapeutics to tumor vasculature in anti-angiogenic cancer therapy. [Copyright &y& Elsevier]

Abstract: Ever since the finding that αvβ3 integrin receptors are over expressed on the endothelial cell surfaces of tumor vasculatures relative to normal resting vasculatures was disclosed in 1994, αvβ3 integrin receptor selective systems are finding increasing applications both for targeting anti-cancer drugs/genes selectively to tumor vasculatures and for imaging growing tumors. Among the cyclic peptide based integrin antagonists identified through both phage display and structure-activity studies, mainly αvβ3 integrin selective cyclic peptide c(RGDfK-) has found most widespread exploitations for targeting chemotherapeutic drugs/genes to both tumor and tumor vasculatures in anti-angiogenic cancer therapy. Herein we show that a lipopeptide containing widely acclaimed αvβ3 integrin receptor selective cyclic RGDfK ligand in its head-group area can effectively deliver genes into both the endothelial and tumor cells via all the three widely used integrin receptors namely αvβ3, αvβ5 & α5β1 integrins. We demonstrate that intravenous administration of the electrostatic complex of the cationic liposomes of an amphiphiles with cyclic RGDfK head-group and the anti-cancer p53 gene leads to significant tumor growth inhibition in a syngeneic mouse tumor model presumably through inducing apoptosis of tumor neovasculatures. The findings delineated herein provide experimental evidence that cyclic-RGDfK-ligand may not be that highly selective for αvβ3 integrin receptor as is popularly believed. [Copyright &y& Elsevier]

Abstract: Re-epithelialization is one of the most important stages of cutaneous regeneration and its success requires supportive micro-ambience which may be provided with suitable bio-matrix. Biocompatibility and efficacy of such bio-matrix in re-epithelialization could be explored by multimodal analysis of structural and functional attributes of in vitro wound healing model including evaluation of prime molecular expressions of the epithelial cells during repair. Present study examines the influence of honey-alginate and alginate matrices on re-epithelialization in keratinocyte (HaCaT) population in a 2-D wound model. Cellular viability, proliferation and cell–cell adhesion status were assessed during wound closure using live/dead cell assay and by evaluating expressions of Ki67, p63 and E-cadherin along-with % change in cellular electrical impedance. Efficacy of honey-alginate matrix in comparison to only alginate one was demonstrated by a quicker reduction in wound gap, improved cellular viability, enhanced expressions of Ki67, p63 and its isoforms (TAp63, ΔNp63) as well as E-cadherin. Faster restoration of electrical attribute (% of impedance change) after wounding also indicated better impact of honey-alginate matrix in re-epithelialization. [Copyright &y& Elsevier]

Abstract: A spectrophotometric method for ascertaining the presence of anionic detergent in milk using azure A dye is described. The method requires brief mixing of milk, azure A dye and EDTA solutions, followed by addition of chloroform and subsequent centrifugation. The blue colour in the chloroform phase was measured at 635 nm. The limits of detection (LOD) and limit of quantification (LOQ) for sodium dodecylbenzene sulfonate in milk were 10 and 20 mg L−1, respectively and for a laboratory grade anionic detergent, labolene, 50 and 100 mg L−1, respectively. Recovery of detergent in spiked milk samples was quantitative. The presence of other additives, i.e., NaOH, NaHCO3, KNO3 and NaCl at levels of 250, 750, 500 and 500 mg L−1 milk, respectively, did not interfere with estimation of detergent. The method is also applicable to milk samples stored in the presence of formalin and sodium azide for 39 days at 4 °C. [Copyright &y& Elsevier]

Abstract: Fresh sub-surface peat samples were collected and palynologically investigated from two different locations at Rajarhat area, N-24Paraganas, 20 km northeast of Kolkata where work was done in connection with building construction. The pollen analytical investigation of the collected peat samples reflected the existence of a large number of core mangroves and some fresh water elements and ferns from a peat layer located at the depth of about 2.2 m–3.5 m below the surface. The present investigation reveals the age of the peat layers ranging from 2665 to 6530 BP, confirming the Holocene age of the samples. The dominant pollen grains recorded from the samples were Heritiera, Excoecaria, Avicennia, Bruguiera, Barringtonia, Rhizophora, Sonneratia, Suaeda, Phoenix paludosa, Nipa and a large number of fern spores including Acrostichum and grass pollen, reflecting a diversity of mangrove vegetation. The variability of the vegetation in the peat from bottom to top shows the change of monsoon months during the Holocene in the BengalBasin. The swampy halophytic vegetation of the Holocene is to some extent comparable to the present day vegetation of the Sunderbans. [ABSTRACT FROM AUTHOR]

The influence of cobalt ion dopant on the in vitro biological properties of biphasic calcium phosphate (BCP) was investigated with an aim to develop an effective scaffold for bone tissue engineering applications. Cost-efficient wet chemical method was used to prepare in-situ cobalt doped BCP and XRD, FTIR, Raman spectroscopy, FESEM analyses were performed for detailed physico-chemical characterizations. It has been observed that pure BCP is comprised of 98 vol% of β-TCP and 2 vol% of β-CPP, whereas incorporation of cobalt leads to 58.8 vol% of β-TCP and 41.4 vol% of β-CPP. Moreover, Co-doped BCP exhibited relatively larger particle size when compared to pure BCP as observed in FESEM analysis. Furthermore, cobalt doped BCP showed enhanced antibacterial activity and the zone of inhibition was prominent compared to pure BCP. The release of cobalt ions from doped BCP was analyzed by Inductively Coupled Plasma (ICP) mass spectrometry at different time points (up to 28 days) and sustained release of cobalt ions warrants its benefits in native tissue regeneration. Both pure and Co-doped BCP showed excellent hemocompatibility as the percentage of hemolysis was below 2 %. Cell viability was found to be marginally higher with incorporation of trace amount of cobalt in BCP. Notably, in vitro angiogenic activity assessment results confirmed that VEGF-A and HIF-1α gene expression was significantly enhanced in case of doped BCP compared to pure BCP, signifying that the cobalt doping considerably improved the expression of angiogenic factors. Over the study, results demonstrated that incorporation of cobalt as dopants can effectively improve the in vitro biological properties of biphasic calcium phosphate based bioceramics and might be considered as a new generation bone grafts in bone regeneration applications. [ABSTRACT FROM AUTHOR]

Among additive manufacturing (AM) techniques, laser or electron beam based processes have been widely investigated for metallic implants. Despite the potential in manufacturing of patient-specific biomedical implants, 3D inkjet powder printing (3DIJPP, a variant of AM) of biomaterials is still in its infancy, as little is known quantitatively about the transient process physics and dynamics. An equally important challenge has been the ink formulation to manufacture biomaterials with reliable mechanical properties and desired biocompatibility. We have developed, for the very first time, the theoretical foundation and experimental formulation of a unique process strategy involving the 'on-demand' delivery of a novel in situ polymerisable acrylic ink system to print a model biomaterial, Ti-6Al-4V. The post-ejection in-flight dynamics of ink droplets have been captured in situ by employing high speed stroboscopic shadowgraphy, to quantitatively estimate the dimensionless numbers of fluid physics for 'printability' assessment. Washburn model was adapted extensively to quantify the capillary ink infiltration time in porous powder bed of finite thickness. On the other hand, particle tracking mode in diffusing wave spectroscopy (DWS) was exploited to analyse the timescale for effective binding of powder particles during in situ polymerisation. The clinically relevant combination of 3D porous architecture with 98.4% interconnectivity among 10–40 μm pores together with modest combination of elastic modulus (4 GPa) and strength reliability (Weibull modulus ∼8.1) establish the potential of inkjet printed Ti-6Al-4V as cortical bone analogue. A better cell attachment, viability, cytoskeletal spreading with pronounced proliferation of murine fibroblasts and pre-osteoblasts on 3DIJPP Ti-6Al-4V, when benchmarked against the metallurgically processed (commercial) or selective laser melted (SLM) Ti-6Al-4V, has been demonstrated, in vitro. The enhanced cellular activities on the 3DIJPP Ti-6Al-4V was explained in terms of an interplay among the elastic stiffness, surface roughness and wettability against the same benchmarking. It is conceived that the quantitative understanding of the integrated process physics and dynamics to print Ti-6Al-4V with reliable mechanical properties together with better cytocompatibility can lead to a paradigm shift in adapting the scalable 3DIJPP for manufacturing of metallic biomaterials. Image 1 [ABSTRACT FROM AUTHOR]

The number of bone damage/fractures has been increasing significantly over the world due to traumatic and accidental injuries. The process of bone regeneration is slowed by oxidative stress at the site of the bone defects. An increase in reactive oxygen species (ROS) is the major cause of oxidative stress. Polymeric scaffolds loaded with free radical scavenging material could be a promising new way to speed up bone healing. The redox-modulating property of cerium oxide (nanoceria) is well-known. In this study, nanoceria was integrated into cellulose-gelatin (CG) and freeze-dried to produce CG-NCs scaffolds. The impact of different concentrations of nanoceria on the physicochemical and biological aspects of scaffolds has also been investigated. FESEM revealed the presence of interconnecting pores in the scaffolds. Furthermore , adding nanoceria to the scaffolds improved mechanical, bio-mineralization properties, and decreased swelling and in-vitro weight loss. In vitro studies confirmed that CG-NCs scaffolds supported cell proliferation and differentiation better than bare (CG) scaffold. The findings of the DPPH assay show that CG-NCs can reduce free radicals. Finally, the antimicrobial evaluations imply that CG-NCs scaffolds successfully inhibited S. aureus and e.coli growth. Thus, the CG-NCs scaffold could offer a lot of potential in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Homeobox (Hox) genes are involved in body plan of embryo along the anterior–posterior axis. Presence of several Hox genes in white adipose tissue (WAT) and brown adipose tissue (BAT) is indicative of involvement of Hox genes in adipogenesis. We propose that differentiation inducing agents viz . isobutyl-methyl-xanthine (IBMX), indomethacin, dexamethasone (DEX), triiodothyronine (T3) and insulin may regulate differentiation in brown adipose tissue through Hox genes. In vitro culture of brown fat stromalvascular fraction (SVF) in presence or absence of differentiation inducing agents was used for establishing relationship between fat accumulation in differentiated adipocytes and expression of Hox genes. Relative expression of Pref1, UCP1 and Hox genes was determined in different stages of adipogenesis. Presence or absence of IBMX, indomethacin and DEX during differentiation of proliferated pre-adipocytes resulted in marked differences in expression of Hox genes and lipid accumulation. In presence of these inducing agents, lipid accumulation as well as expression of HoxA1, HoxA5, HoxC4 & HoxC8 markedly enhanced. Irrespective of presence or absence of T3, insulin down regulates HoxA10 . T3 results in over expression of HoxA5, HoxC4 and HoxC8 genes, whereas insulin up regulates expression of only Hox C8. Findings suggest that accumulation of fat in differentiated adipocytes is linked with expression of Hox genes. [ABSTRACT FROM AUTHOR]

Accelerating the clearance of intracellular protein aggregates through elevation of autophagy represents a viable approach for the treatment of neurodegenerative diseases. In our earlier report, we have demonstrated the enhanced degradation of mutant huntingtin protein aggregates through autophagy process induced by europium hydroxide nanorods [EHNs: Eu III (OH) 3 ], but the underlying molecular mechanism of EHNs mediated autophagy was unclear. The present report reveals that EHNs induced autophagy does not follow the classical AKT-mTOR and AMPK signaling pathways. The inhibition of ERK1/2 phosphorylation using the specific MEK inhibitor U0126 partially abrogates the autophagy as well as the clearance of mutant huntingtin protein aggregates mediated by EHNs suggesting that nanorods stimulate the activation of MEK/ERK1/2 signaling pathway during autophagy process. In contrast, another mTOR-independent autophagy inducer trehalose has been found to induce autophagy without activating ERK1/2 signaling pathway. Interestingly, the combined treatment of EHNs and trehalose leads to more degradation of mutant huntingtin protein aggregates than that obtained with single treatment of either nanorods or trehalose. Our results demonstrate the rational that further enhanced clearance of intracellular protein aggregates, needed for diverse neurodegenerative diseases, may be achieved through the combined treatment of two or more autophagy inducers, which stimulate autophagy through different signaling pathways. [ABSTRACT FROM AUTHOR]

In the present article, we demonstrate the delivery of anti-cancer drug to the cancer cells using biosynthesized gold and silver nanoparticles (b-AuNP & b-AgNP). The nanoparticles synthesized by using Butea monosperma ( BM ) leaf extract are thoroughly characterized by various analytical techniques. Both b-AuNP and b-AgNP are stable in biological buffers and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2 & A549). Administration of nanoparticle based drug delivery systems (DDSs) using doxorubicin (DOX) [b-Au-500-DOX and b-Ag-750-DOX] shows significant inhibition of cancer cell proliferation (B16F10, MCF-7) compared to pristine drug. Therefore, we strongly believe that biosynthesized nanoparticles will be useful for the development of cancer therapy using nanomedicine approach in near future. [ABSTRACT FROM AUTHOR]

The paper deals with the analyses of the atmospheric vertical potential gradient (PG) from the ground for 90 fair weather days during 2006–2009 measured at Kolkata (Lat: 22.56°N). The variations of PG have been studied extensively to investigate their values during monsoon and winter seasons. Higher values of PG at Kolkata are observed due to higher abundance of pollutant particles. The observed PG are compared with the results of Potsdam station (Lat: 52°N) and Johannesburg station (Lat: 26°S), with 9 years data and 2 years data respectively. The correlations studies are carried out among PG, PDC (Point Discharge Current) as well as negative and positive carrier conductivities. The corresponding correlation coefficients are obtained as 0.93, −0.842 and −0.844. [ABSTRACT FROM AUTHOR]

Abstract: In this paper an attempt is made to study the Einstein relation for the diffusivity-mobility ratio (DMR) in nonlinear optical compounds on the basis of a newly formulated electron energy spectrum taking into account the combined influences of the anisotropies in the effective electron mass and the spin orbit splitting constant together with the inclusion of crystal field splitting in the Hamiltonian within the framework of k.p formalism. The corresponding results for III–V, ternary and quaternary types of optoelectronic materials form a special case of our generalized analysis. We have also studied the DMR in II–VI, Bi, IV–VI and stressed materials on the basis of various band models as applicable for such specialized materials. It has been found taking n-Cd3As2, n-CdGeAs2, n-InAs, n-InSb, n-Hg1− x Cd x Te and n-In1− x Ga x As y P1− y lattice matched to InP, CdS, Bi, PbS, PbTe, PbSe and stressed InSb as examples of the aforementioned compounds that the DMR increases with increasing electron concentration in various manners and the rate of increase is greatly influenced by the presence of the different energy band constants of the said materials together with the fact that the rates of variation are totally band structure dependent. An experimental method of determining the DMR in degenerate samples having arbitrary dispersion laws has been suggested and the present simplified analysis is in agreement with the suggested relationship. In addition, the well-known results for nondegenerate wide gap materials have been obtained as special cases of our generalized theory under certain limiting conditions. [Copyright &y& Elsevier]

• Remodeling of mitochondria and mitochondrial functionality is an eminent factor in cellular life and death. • Dysfunctions of mitochondrial functions and apoptosis pathway are associated with pathological process in cancer. • We investigated a prognostic significance of Drp1 in a clinic-pathological study. • ROS mediated up-regulated mitochondrial mass and shift in mitochondrial fission. • Bcl-2 mediated mitochondrial fission promoting up-regulation of cell cycle marker CyclinD1 in cancer cells. Dysregulation in mitochondrial dynamics has been associated with several diseases including cancer. Present study assessed the alteration in mitochondrial fission protein (Drp1) in oral epithelial cells collected from clinically confirmed pre-cancer and cancer patients and further correlates it with the cellular apoptosis signaling. Results indicate the ROS accumulation in OSCC patients is accompanied by several changes including increase in mitochondrial mass, expression of mitochondrial fission protein (Drp1) and alteration in apoptotic signaling. The positive co-relation has been observed between the expressions of anti-apoptotic Bcl-2proteinswith mitochondrial fission protein Drp1. Higher mitochondrial fission in oral cancer cells was also correlated with the increased expression of cell cycle marker CyclinD1 indicating highly proliferative stage of oral cancer cells. The clinical correlation can be extended to develop biomarker for diagram and program in oral cancer management. [ABSTRACT FROM AUTHOR]

Tobacco smoking is considered as one of the major risk factors for development of oral cancer. In vitro studies indicate that cigarette smoke initiates transformation of epithelial cells toward development of oral cancer through altering mitochondrial metabolic pathways. However the present in vitro models need to be improved to correlate these molecular changes with epithelial transformations. In present study, we investigated the association of mitochondrial metabolic events with oral cancer progression under cigarette smoke extract (CSE). In this regard, an in vitro model of oral keratinocyte cell line (MOE1A) was developed by exposing them with different concentrations of CSE. Alterations in cellular phenomena were confirmed by Fourier-transform infrared spectroscopy (FTIR) study, which indicated changes in important functional groups of CSE-induced oral cells. Enhanced reactive oxygen species (ROS) of exposed cells altered the mitochondrial metabolic activities in terms of increased mitochondrial mass and DNA content. Further, mitochondrial heme-metabolism was investigated and real-time PCR study showed altered expression of important genes like ALAS1, ABCB6, CPOX, FECH, HO-1. Both transcriptomic and proteomic studies showed up- and down-regulation of important biomarkers related to cellular cancer progression. Overall data suggest that CSE alters mitochondrial heme metabolic pathway and initiates cancer progression through modifying cellar biomarkers in oral epithelial cells. Schismatic represents CSE exposure increased cytotoxicity and cell death through ROS generation in oral keratinocyte cells. Increased ROS generation altered oxidative stress and mitochondrial bioenergetics via increasing heme production and expression of heme oxygenase (HO-1) gene. Enhanced ROS developed epithelial to mesenchymal transition (EMT) through disturbing cell-cell junction and imitated metastasis and cell death. Unlabelled Image • Cigarette smoke extract (CSE) induced cytotoxicity on oral epithelial cells. • CSE enhanced oxidative stress by increasing ROS. • CSE increased mitochondrial mass and DNA content. • CSE altered mitochondrial heme metabolic pathway under high oxidative stress. • CSE may initiate oral cancer progression through induction of EMT. [ABSTRACT FROM AUTHOR]

Cell-free and cell-loaded constructs are used to bridge the critical-sized bone defect. Oxidative stress at the site of the bone defects is a major interference that slows bone healing. Recently, there has been an increase in interest in enhancing the properties of three-dimensional scaffolds with free radical scavenging materials. Cerium oxide nanoparticles (CNPs) can scavenge free radicals due to their redox-modulating property. In this study, freeze-drying was used to fabricate CG-CNPs nanocomposite scaffolds using gelatin (G), chitosan (C), and cerium oxide nanoparticles. Physico-chemical, mechanical, and biological characterization of CG-CNPs scaffolds were studied. CG-CNPs scaffolds demonstrated better results in terms of physicochemical, mechanical, and biological properties as compared to CG-scaffold. CG-CNPs scaffolds were cyto-friendly to MC3T3-E1 cells studied by performing in-vitro and in-ovo studies. The scaffold's antimicrobial study revealed high inhibition zones against Gram-positive and Gram-negative bacteria. With 79 % porosity, 45.99 % weight loss, 178.25 kPa compressive modulus, and 1.83 Ca/P ratio, the CG-CNP 2 scaffold displays the best characteristics. As a result, the CG-CNP 2 scaffolds are highly biocompatible and could be applied to repair bone defects. [ABSTRACT FROM AUTHOR]

Ethnopharmacology relevance In traditional medicines honey is known for healing efficacy and vividly used as “Anupan” in Ayurvedic medicines appreciating roles in dilutions. Validating efficacy of physico-chemically characterized honey in dilutions, studies on in vitro wound healing and attainment of cellular confluence epithelial cells including expressions of cardinal genes is crucial. To evaluate effects of characterized honey in varied dilutions on cellular viability, in vitro wound healing and modulation of prime epithelial gene expressions. Materials and methods Six Indian honey-samples from different sources were physico-chemically characterized and optimal one was explored in dilutions (v/v%) through in vitro studies on human epithelial (HaCaT) cells for viability, wound healing and expressions of genes p63, E-cadherin, β-catenin, GnT-III and GnT-V. Results Studied honey samples ( i.e . A–F) depicted range of pH (2–4), water (12.48–23.95), electrical conductivity (2.57–14.34), carbohydrate (68.73–98.65), protein (.316–5.36) and antioxidant potential. Though sample A and F showed physico-chemical proximity, but overall bio-impact of the earlier was better, thus studied in 8–.1% (v/v) dilution range. Four dilutions (.01, .04, .1, .25 v/v%) augmented cellular viability but in vitro wound healing was fastest ( p <.05) under .1%. Such efficacy was further documented for p63 up-regulation by immunocytochemistry and mRNA studies. The E-cadherin and β-catenin mRNA-expressions were also up-regulated and their proteins were predominantly cytoplasmic. E-cadherin up-regulation was corroborative with down-regulation and up-regulation of GnT-III and GnT-V respectively. Conclusion Present study illustrated efficacy of particular honey dilution (.1%) with characteristic free radical scavenging activity in facilitating cell proliferation and attainment of confluence towards faster wound healing and modulation of cardinal epithelial genes ( viz. p63, E-cadherin, β-catenin, Gnt-III and V). [ABSTRACT FROM AUTHOR]

Abstract: Autophagy is one of the well-known pathways to accelerate the clearance of protein aggregates, which contributes to the therapy of neurodegenerative diseases. Although there are numerous reports that demonstrate the induction of autophagy with small molecules including rapamycin, trehalose and lithium, however, there are few reports mentioning the clearance of aggregate-prone proteins through autophagy induction by nanoparticles. In the present article, we have demonstrated that europium hydroxide [EuIII(OH)3] nanorods can reduce huntingtin protein aggregation (EGFP-tagged huntingtin protein with 74 polyQ repeats), responsible for neurodegenerative diseases. Again, we have found that these nanorods induce authentic autophagy flux in different cell lines (Neuro 2a, PC12 and HeLa cells) through the expression of higher levels of characteristic autophagy marker protein LC3-II and degradation of selective autophagy substrate/cargo receptor p62/SQSTM1. Furthermore, depression of protein aggregation clearance through the autophagy blockade has also been observed by using specific inhibitors (wortmannin and chloroquine), indicating that autophagy is involved in the degradation of huntingtin protein aggregation. Since [EuIII(OH)3] nanorods can enhance the degradation of huntingtin protein aggregation via autophagy induction, we strongly believe that these nanorods would be useful for the development of therapeutic treatment strategies for various neurodegenerative diseases in near future using nanomedicine approach. [Copyright &y& Elsevier]